HBV Infection of Human Hepatocytes in Immunocompetent Rodents

In order to permit immune acceptance of human ceils without generalized immunosuppression, groups of normal fetal rats at 17 days of gestation were inoculated ip with primary human hepatocytes by intra-intrauterine injection. One day after birth, suspensions of primary human hepatocytes were transplanted via intrasplenic injection. One week later, groups of rats were inoculated with infectious hepatitis B virus (HBV). Tolerized rats that were transplanted with human hepatocytes and subsequently infected with HBV, had hepatitis B surface antigen (HBsAg) detectable in serum beginning on day 3,     

Proliferation of L02 human hepatocytes in tolerized genetically immunocompetent rats

AIM： To investigate whether human hepatocytes could proliferate after transplantation to normal immunocompetent rats treated with 2-acetaminofluorene or Retrorsine and partial hepatectomy. METHODS： L02 hepatocyte-tolerant Sprague-Dawley rats were injected with Retrorsine, 2-acetaminofluorene or normal saline. L02 hepatocytes were then transplanted via the spleen. Human albumin and its mRNA, specific proliferating cell nuclear antigen （PCNA）, L02 hepatocyte dynamic distribution, number density and area density of PCNA-positive cells in the liver were determined. RESULTS： All the examined indicators were not significantly different between the rats treated with 2-acetaminofluorene and normal saline, which was not the case with rats treated with Retrorsine. A dynamic distribution of L02 hepatocytes in the rat liver was detected from wk 1 to mo 6 after transplantation in the Retrorsine group and from wk 1 to 10 in the 2-acetaminofluorene group. Human albumin and its mRNA were detected from wk 2 to mo 6 in the Retrorsine group and from wk 1 to 8 in the 2-acetaminofluorene group. Specific human PCNA was detected in the rat liver from wk 2 to mo 6 in the Retrorsine group and from wk 2 to 6 in the 2-acetaminofluorene group. Human albumin and its mRNA contents as well as the number of PCNA positive cells reached a peak at wk 4. CONCLUSION： L02 human hepatocytes could not proliferate significiantly after transplantation to the normal, immunocompetent rats treated with 2-acetaminofluorene.L02 human hepatocytes can survive for 10 wk after transplantation and express human albumin for 8 wk. L02 human hepatocytes can proliferate and express human albumin for 6 mo after transplantation to the rats treated with Retrorsine. The chimeric L02 human hepatocytes, which then underwent transplantation into tolerant rats, were normal in morphogenesis, biochemistry and function.     

Effect of jianpiyiwei capsule on gastric precancerous lesions in rats

AIM：To evaluate the therapeutic effect of compound Chinese drugs,Jianpiyiwei capsule(JPYW)on gastric precancerous lesions in rats and to explore its mechanism of action.METHODS:Model of gastric precancerous lesions was constructed in male Wistar rats:a metal spring was inserted and fixed through pyloric sphincter.One week after recovery,each rat was given50-60℃hot paste containing150g/LNaCl2mLorally,twice a week for 15weeks.Then10normal and11model rats were anaesthetized,after the measurement of gastric mucosa blood flow(GMBF),the rats were killed and the mucosal hexosamines and malonic dialdehyde(MDA)were measured.The morphological changes of gastric mucosa were observed macroscopically and microscopically,and by an automatic imaging analysis system.Other rats were treated with JPYW1.5g/kg-d^·1 0r4.5g/kg·d^-1.ordistilled water as negative control respectively(n=10in each group).After 12weeks,all the rats were examined as above.RESULTS:The gastric mucosa of model rats showed chronic atrophic gastritis with dysplasia and intestinal metaplasia(IM).GMBFand hexosamine content were reduced significantly and MDAwas increased as compared to the normal group(P<0.01).After12weeks treatment,the pathological changes of the negative control group became worsened.while in JPYWtreated groups the changes were modified with significant increase of GMBF and reduction of MDA,although the hexosamine concentration increased only mildly.CONCLUSION:JPYW increases GMBFand reducesMDAcontent in gastric mucosa and has therapeutic effects on gastric precancerous lesions.     

Effects of electroacupuncture at “Zusanli” (ST 36)on expression of mitophagy-related proteins in skeletal muscle in rats with spleen deficiency syndrome

正Objective To observe the expression change of mitophagy-related proteins in skeletal muscle in rats with spleen deficiency syndrome and to explain the partial action mechanism of acupuncture at Zusanli (ST 36) for spleen deficiency syndrome.Methods Forty male SD rats, after normal feeding, were randomly divided into a normal group, a spleen deficiency group, a Zusanli group and a non-acupoint group, ten rats in each group.Except the normal group, the three factors modeling method was used for 14 days to establish the model of     

Possible ameliorative effect of breastfeeding and the uptake of human colostrum against coeliac disease in autistic rats

AIM: To examine the possible ameliorative effect of breastfeeding and the uptake of human colostrum against coeliac disease in autistic rats. METHODS: Female rats were fed a standard diet and received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception. In study 1, neonatal rats were randomly subjected to blood tests to investigate autism. In study 2, the 1st group was fed by the mother after an injection of interferon-γ (IFN-γ) and administration of gliadin. The pups in the 2nd group were prevented from accessing maternal milk, injected IFN-γ, administered gliadin, and hand-fed human colostrum. The normal littermates fed by the table mothers were injected with physiological saline and served as normal controls in this study.RESULTS: The protein concentration was higher in group 2 than in group 1 in the duodenum (161.6 ± 9 and 135.4 ± 7 mg/g of tissue, respectively, P < 0.01). A significant increase (P < 0.001) in body weight was detected in human colostrum-treated pups on post natal day (PND) 7 and 21 vs suckling pups in group 1. A delay in eye opening was noticed in the treated rats in group 1 on PND 13 compared with the control group and group 2. Administration of a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception resulted in significantly reduced calcium and vitamin D levels in study 1 compared with the control groups (P < 0.001). However, human colostrum uptake inhibited increases in the level of transglutaminase antibody in autistic pups with coeliac disease. CONCLUSION: The effects of early-life nutrition and human colostrum on the functional maturation of the duodenal villi in autistic rats with coeliac disease that might limit or prevent the coeliac risk with autism.     

Expression and location of Smad2, 4 mRNAs during and after liver fibrogenesis of rats

AIM: To investigate the location alteration of Smad2 and Smad4 mRNAs in the liver during and after fibrogenesis in rats. METHODS: Eighty male Wistar rats weighing approximately 200 g each were used. The rat models of experimental hepatic fibrosis were established by injection with carbon tetrachloride (CCl4), normal rats and rats were injected with olive oil and served as control groups. In situ hybridization(ISH) was used to detect the Smad2 and Smad4 mRNA in liver. RESULTS: In situ hybridization showed Smad2 and Smad4 mRNA expressions in the cytoplasm of hepatic stellate cells (HSC), fibroblasts and myofibroblasts around the central vein and hepatic sinus during and after fibrogenesis. Expression of Smad2, 4 mRNA was higher than that in normal and control rats. CONCLUSION: In the process of and after hepatic fibrosis formation, HSC, fibroblasts and myofibroblasts are the major cells that express Smad2 and Smad4. The more serious the hepatic fibrosis is in the injured liver, the higher the level of Smad2 and Smad4 gene expression is during and after fibrogenesis respectively.     

Relationship between entero-hepatic bile acid circulation and interdigestive migrating myoelectrical activity in rats

AIM: To investigate the effects of entero-hepatic bile acid circulation on the inter-digestive migrating myoelectrical complex (MMC) in rats. METHODS: Thirty-two rats were divided into four groups. Three pairs of bipolar silver electrodes were chronically implanted in the antrum, duodenum and jejunum. Three groups of them were ligated around the upper part of common bile duct (CBD). The experiments were performed in conscious and fasting state. The gastrointestinal myoelectrical activity was recorded. Ursodeoxycholic acid (UDCA) and saline were then perfused into stomachs of two groups with CBD obstruction and the effects of them on the MMC were observed. RESULTS: A typical pattern of MMC was observed in normal fasting rats. MMC of antral and duodenal origin disappeared temporarily in earlier stage of CBD obstruction. While MMC of jejunum origin appeared. increased MMC cycle duration was seen after 4 d in rats with CBD obstruction. The MMC after CBD obstruction was characterized by an increased duration of phase Ⅱ-like activity and decreased duration of phase Ⅰ & Ⅲ activity. Perfusion into stomachs with UDCA resulted in a shorter MMC cycle duration and a longer duration of phase Ⅲ of duodenal origin compared to the normal group. CONCLUSION: Entero-hepatic bile acid circulation initiates inter-digestive MMC of duodenal origin.     

Enteral feeding of glycyl-glutamine dipeptide improves the structure and absorptive function of the small intestine after allogenetic liver transplantation in rats

BACKGROUND: Recipients of liver transplantation could have postoperative structural injury and declined absorptive function in the gastrointestinal tract. Glutamine (Gln) is a special nutrient of small intestinal mucosa and of various kinds of cells proliferating rapidly. But Gln could form a kind of poisonous pyroglutamic acid in water solution, which is the limitation of Gln in clinical practice. Glycyl-glutamine (Gly-Gln) is highly soluble and can be hydro-lyzed to release glutamine. This study was undertaken to observe the effect of Gly-Gln dipeptide by enteral feeding on the intestinal structure and absorptive function after allogenetic liver transplantation in rats. METHODS: Twelve male inbred Lewis rats were selected randomly as donors, and 24 male inbred BN rats as recipients of allogenetic liver transplantation. The recipients were also randomly divided into two groups; control group (ALA group, n = 12 ) and experimental group ( GLN group , n =12). In each group, 6 normal BN rats were sampled as the normal parameter on the 3rd preoperative day. The 6 recipients in the control group received alanine 0. 6 g/kg daily for 3 days before operation and 7 days after operation by gastric perfusion, and the 6 recipients in the experimental group were given Gly-Gln 0.6 g/kg daily the same way. The 12 BN recipients underwent 3-day fasting (free access to water with 0. 23% sodium chloride) and ortho-topic liver transplantation in aseptic conditions and were given subcutaneous injection of CsA 2 mg/kg daily after the operation. The 12 BN recipients were sampled on the 8th postoperative day. All of the 24 BN rats were subjected to examination of mucosal structure, activities of Na + -K + - ATP and disaccharidase, and D-xylose absorption test. RESULTS: The 12 BN recipients were alive after liver transplantation. On the 3rd preoperative day, mucosal structure , activities of Na + -K -ATP and disaccharidase and D-xylose absorption in the two groups were not significantly different. On the 8th postoperative day, the parameters of the two groups were markedly changed compared with those on the 3rd preoperative day. However, the parameters of GLN group were remarkably higher than those of ALA group. CONCLUSION: Enteral feeding of Gly-Gln could improve the structure and absorptive function of the small intestine after liver transplantation in rats.     

Expression of intestinal trefoil factor, proliferating cell nuclear antigen and histological changes in intestine of rats after intrauterine asphyxia

AIM: To study the expressions of intestinal trefoil factor (ITF) and proliferating cell nuclear antigen (PCNA) and histologic changes in intestine, to investigate the relationship between ITF and intestinal damage and repair after intrauterine hypoxia so as to understand the mechanism of intestinal injury and to find a new way to prevent and treat gastrointestinal diseases. METHODS: Wistar rats, pregnant for 21 d, were used to establish animal models of intrauterine asphyxia by clamping one side of vessels supplying blood to uterus for 20 min, another side was regarded as sham operation group. Intestinal tissues were taken away at 0, 24, 48 and 72 h after birth and stored in different styles. ITF mRNA was detected by RT-PCR. PCNA expression was measured by immunohistochemistry. Intestinal tissues were studied histologically by HE staining in order to observe the areas and degree of injury and to value the intestinal mucosa injury index (IMDI). RESULTS: ITF mRNA appeared in full-term rats and increased with age. After ischemia, ITF mRNA was decreased to the minimum (0.59?.032) 24 h after birth, then began to increase higher after 72 h than it was in the control group (P<0.01). PCNA positive staining located in goblet cell nuclei. The PCNA level had a remarkable decline (53.29±1.97) 48 h after ischemia. Structure changes were obvious in 48-h group, IMDI (3.40±0.16) was significantly increased. Correlation analyses showed that IMDI had a negative correlation with ITF mRNA and PCNA (r= -0.543, P<0.05; r= -0.794, P<0.01, respectively). CONCLUSION: Intrauterine ischemia can result in an early decrease of ITF mRNA expression. ITF and PCNA may play an important role in the damage and repair of intestinal mucosa.     

Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats

AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intraven ously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals. RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the most effective group after four times of injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The level of serum AST and ALT remarkably reduced in recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The results showed that the effect of 200 μg/kg recombinant pcDNA3-ALR plasmid in the rats with acute liver injury was stronger than that of 50 μg/kg pcDNA3-ALR DNA. The effect of intravenous injection of recombinant pcDNA3 ALR plasmid was better. After the rats with acute hepatic failure were treated with recombinant pcDNA3-ALR plasmid, the survival rate (40%) significantly increased in treatment groups compared to control group (15%, P<0.01). CONCLUSION: The ALR gene may play an important role in relieving acute hepatic injury and hepatic failure by promoting hepatic cell proliferation and reducing level of AST and ALT in CCl4-intoxicated rats.     

Effect of Egyptian propolis on cryptosporidiosis in immunosuppressed rats with special emphasis on oocysts shedding,leukogram,protein profile and ileum histopathology

Objective:To investigate the activity of Egyptian propolis extracts(ethanol and water)on cryptosporidiosis in experimentally infected dexamethasone-immunosuppressed rats.Methods:A total of 180 male rats(190-220)g BWt were randomly divided into 9 equal groups(G1-G9).Groups of rats were kept as(G1):normal control,(G2-G9):immunosuppressed with dexamethasone and(G3-G9):infected with Cryptosporidium oocysts.Rats from(G4to G9)were given orally ethanol and water extract of propolis(at a dose of 50 mg/kg BWt)and nitazoxanide(standard anti-cryptosporidial drug at a dose of 100 mg/kg BWt)to infected rats with different regimes.Faecal pellets were collected from all groups to monitor oocysts shedding from the 2nd to the 15th day post infection.At the end of the experiment,blood was collected from all groups for determination of leukogram and serum proteins.Ileum specimens were also examined histopathologically.Results:The highest reduction of oocysts shedding in faecal samples was 88%in rats prophylactically treated with propolis ethanol extract at the 4th dpi,and in rats prophylactically treated with water extract of propolis,was91%at the 6th dpi.There was a marked increase in neutrophils count and α_2-andβ-globulins levels in infected rats treated with both extracts,while a significant decrease was detected in lymphocytes compared to the infected non treated group.β-globulin level markedly increased in the rats administered nitazoxanide.Histopathological changes were observed in the ileum of rats infected with Cryptosporidium.Conclusions:Egyptian propolis extracts have an activity on cryptosporidiosis in rats.Moreover,propolis modulated the immunity in dexamethasone-immunosuppressed rats.     

Effect of environmental hyperthermia on gastrin, somatostatin and motilin in rat ulcerated antral mucosa

AIM: To study the effect of environmental hyperthermia on gastrin, somatostatin and motilin in rat ulcerated antral mucosa.METHODS: Forty-two Wistar rats were equally divided into six groups, according to the room temperature (high and normal) and the treatment (acetic acid, normal saline and no treatment). Levels of gastrin, somatostatin and motilin in rat ulcerated antral mucosa were measured with a radioimmunoassay method.RESULTS: The average temperature and humidity were 32.5℃ and 66.7% for the high temperature group, and 21.1℃ and 49.3% for the normal temperature group,respectively. Gastric ulcer model was successfully induced in rat injected with 0.05 mL acetic acid into the antrum. In rats with gastric ulcers, the levels of gastrin and motilin increased, whereas the somatostatin level declined in antral mucosa, compared with those in rats treated with normal saline and the controls. However, the change extent in the levels of gastrin, motilin and somatostatin in antral mucosa was less in the high temperature group than in the normal temperature group.CONCLUSION: The levels of gastrin, somatostatin and motilin in rat ulcerated antral mucosal tissue remain relatively stable in a high temperature environment, which may relate to the equilibration of the dynamic system.     

Effect of Sinai san decoction on the development of non-alcoholic steatohepatitis in rats

AIM: To explore the effect of Sinai san decoction on the development of non-alcoholic steatohepatitis induced by CCL4 combined with a fat-rich diet in rats. METHODS: Twenty-seven Sprague-Dawley rats were divided into three groups randomly: control group (n=9), model group (n = 9) and treatment group (n = 9). The rats of model group and treatment group were given small dosage of CCL4 combined with a fat-rich diet, and those of control group were given normal diet. After four weeks of fat-rich diet feeding, the rats of treatment group were given Sinai san decoction. The serum levels of aminotransferase and lipid were measured, and the pathology of livers was observed by HE staining after the rats were sacrificed at eight weeks. RESULTS: The rats' livers presented the pathology of steatosis and inflammation with higher serum levels of ALT and AST in the model group. In the treatment group the serum ALT and AST levels decreased significantly and were close to the control group. The hepatic inflammation scores also decreased markedly, but were still higher than those of control group. And the degree of hepatocyte steatosis was similar to that of model group. CONCLUSION: Sinai san decoction may ameliorate the hepatic inflammation of rats with steatohepatitis induced by small dosage of CCL4 combined with a fat-rich diet, but does not prevent the development of hepatocyte steatosis.     

Adenoviral transfer of human interleukin-10 gene in lethal pancreatitis

AIM: To evaluate the therapeutic effect of adenoviral-vector-delivered human interleukin-10 (hIL-10) gene on severe acute pancreatitis (SAP) rats. METHODS: Healthy Sprague-Dawley (SD) rats were intraperitoneally injected with adenoviral IL-10 gene (AdvhIL-10), empty vector (Adv0) or PBS solution. Blood, liver, pancreas and lung were harvested on the second day to examine hIL-10 level by ELISA and serum amylase by enzymatic assay. A SAP model was induced by retrograde injection of sodium taurocholate through pancreatic duct. SAP rats were then administered with AdvhIL-10, Adv0and PBS solution by a single intraperitoneal injection 20 min after SAP induction. In addition to serum amylase assay, levels of hIL-10 and tumor necrosis factor-α (TNF-α) were detected by RT-PCR, ELISA and histological study. The mortality rate was studied and analyzed by Kaplan-Meier and log rank analysis.RESULTS: The levels of hIL-10 in the pancreas, liver and lung of healthy rats increased significantly after AdvhIL-10 injection (1.42 ng/g in liver, 0.91 ng/g in pancreas); while there was no significant change of hIL-10 in the other two control groups. The concentration of hIL-10 was increased significantly in the SAP rats after AdvhIL-10 injection (1.68 ng/g in liver, 1.12 ng/g in pancreas) compared to the other two SAP groups with blank vector or PBS treatment (P&lt;0.05). The serum amylase levels remained normal in the AdvhIL-10 transfected healthy rats. However, the serum amylase level was significantly elevated in the other two control SAP rats. In contrast, serum amylase was down-regulated in the AdvhIL-10 treated SAP groups.The TNF-α expression in the AdvhIL-10 treated SAP rats was significantly lower compared to the other two control SAP groups. The pathohistological changes in the AdvhIL-10 treated group were better than those in the other two control groups. Furthermore, the mortality of the AdvhIL-10 treated group was significantly reduced compared to the other two control groups (P&lt;0.05). CONCLUSION: Adenoviral hIL-10 gene can significantly attenuate the severity of SAP rats, and can be used in the treatment of acute inflammation process.     

Indomethacin but not a selective cyclooxygenase-2 inhibitor inhibits esophageal adenocarcinogenesis in rats

AIM:To evaluate the effects of indomethacin [dual cyclooxygenase(COX)-1/COX-2 inhibitor] and 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl) phenyl)2-(5H)-furanone(MF-tricyclic)(COX-2 selective inhibitor) in a rat experimental model of Barrett's esophagus and esophageal adenocarcinoma.METHODS:A total of 112 surviving post-surgery rats were randomly divided into three groups:the control group(n = 48),which did not receive any treatment;the indomethacin group(n = 32),which were given 2 mg/kg per day of the COX-1/COX-2 inhibitor;and the MF-tricyclic group(n = 32),which received 10 mg/kg per day of the selective COX-2 inhibitor.Randomly selected rats were killed either 8 wk or 16 wk after surgery.The timing of the deaths was in accordance with a previous study performed in our group.Only rats that were killed at the times designated by the protocol were included in the study.We then assessed the histology and prostaglandin E2(PGE2) expression levels in the rat esophagi.An additional group of eight animals that did not undergo esophagojejunostomy were included in order to obtain normal esophageal tissue as a control.RESULTS:Compared to a control group with no treatment(vehicle-treated rats),indomethacin treatment was associated with decreases in ulcerated esophageal mucosa(16% vs 35% and 14% vs 17%,2 mo and 4 mo after surgery,respectively;P = 0.021),length of intestinal metaplasia in continuity with anastomosis(2 ± 1.17 mm vs 2.29 ± 0.75 mm and 1.25 ± 0.42 mm vs 3.5 ± 1.54 mm,2 mo and 4 mo after surgery,respectively;P = 0.007),presence of intestinal metaplasia beyond anastomosis(20% vs 71.4% and 0% vs 60%,2 mo and 4 mo after surgery,respectively;P = 0.009),severity of dysplasia(0% vs 71.4% and 20% vs 85.7% high-grade dysplasia,2 mo and 4 mo after surgery,respectively;P = 0.002),and adenocarcinoma incidence(0% vs 57.1% and 0% vs 60%,2 mo and 4 mo after surgery,respectively;P 0.0001).Treatment with the selective COX-2 inhibitor,MF-tricyclic,did not prevent development of intestinal metaplasia or adenocarcinoma.In parallel,we observed a significant decrease in PGE2 levels in indomethacin-treated rats,but not in those treated with MF-tricyclic,at both 2 mo and 4 mo.Compared to control rats that did not undergo surgery(68 ± 8 ng/g,P = 0.0022 Kruskal-Wallis test) there was a significant increase in PGE2 levels in the esophageal tissue of the rats that underwent surgery either 2 mo(1332 ± 656 ng/g) or 4 mo(1121 ± 1015 ng/g) after esophagojejunostomy.However,no differences were found when esophageal PGE2 levels were compared 2 mo vs 4 mo post-esophagojejunostomy.At both the 2-and 4-mo timepoints,we observed a significant decrease in PGE2 levels in indomethacin-treated rat esophagi compared to those in either the control or MF-tricyclic groups(P = 0.049 and P = 0.017,respectively).No differences in PGE2 levels were found when we compared levels in rats treated with MF-tricyclic to not-treated rats.CONCLUSION:In this rat model of gastrointestinal reflux,indomethacin was associated with a decrease in the severity of esophagitis and reduced development of esophageal intestinal metaplasia and adenocarcinoma.     

Changes of biological functions of dipeptide transporter （PepT1） and hormonal regulation in severe scald rats

AIM: To determine the regulatory effects of recombinant human growth hormone (rhGH) on dipeptide transport (PepT1) in normal and severe scald rats. METHODS: Male Sprague-Dawley rats with 30 % total body surface area (TBSA) III degree scald were employed as the model. In this study rhGH was used at the dose of 2 IU.kg^1.d^-1 An everted sleeve of intestine 4 cm long obtained from mid-jejunum was securely incubated in Kreb‘s solution with radioactive dipeptide (3H-glycylsarcosine, 3H-Gly-Sar,10μCi/ml) at 37℃ for 15 min to measure the effects of uptake and transport of PepT1 of small intestinal epithelial cells in normal and severe scald rats. RESULTS: Abundant blood supply to intestine and mesentery was observed in normal and scald rats administered rhGH, while less supply of blood to intestine and mesentery was observed in rats without rhGH. Compared with controls, the transport of dipeptide in normal rats with injection of rhGH was not significantly increased (P=-0.1926), while the uptake was significantly increased (P=-0.0253). The effects of transport and uptake of PepT1 in scald rats with injection of rhGH were significantly increased (P=0.0082, 0.0391). CONCLUSION: Blood supply to intestine and mesentery of rats was increased following injection of rhGH. The effectsof uptake and transport of dipeptide transporters in small intestinal epithelial cells of rats with severe scald were markedly up-regulated by rhGH.     

Time-effect relationship and molecular mechanism of electroacupuncture for repair of gastric mucosal lesion

正Objective To dynamically observe the effects o electroacupuncture (EA) on repair of gastric mucosal lesion in rats with gastric ulcer, and to explore the timeeffect relationship and molecular mechanism of EA for gastric ulcer.Methods A total of 72 SD rats were randomly assigned to a normal group, a model group, a acupoint group and a sham acupoint group, and each group were further divided into a 1-day subgroup, a 4-day subgroup and a 7-day subgroup, 6 rats in each subgroup.The rat model of gastric ulcer was established by using intragastric administration of ethyl alcohol. The rats in the acupoint group were treated with EA at "Zusanli"(ST 36) and "Liangmen"(ST 21); the rats in the sham acupoint group were treated with EA at points 5 mm nex     

Effect of captopril on serum TNF-α level in acute lung injury rats induced by HCL

Objective:To observe the effect of captopril on the tumor necrosis factor-α(TNF- α) level and arterial blood gases in acute lung injury(All) induced by HCL in rats,and to analyze its protective mechanism.Methods:Fifty Wistar rats were selected and randomly divided into three groups,with 20 rats in Group Ⅰ and Ⅱ,respectively and 10 animals in Group Ⅲ.ALI model was constructed by intratracheal injection of diluted hydrochloric acid(pH=1.25.1.2 mL/kg).Group Ⅰrats received not any treatment after construction of AM model.Group Ⅱ rats were treated with captopril(5 mg/kg,i.p.) 5 min after induction of ALI.Group Ⅲ served as normal control without any treatment.Ninety minutes after construction of ALI model,all the rats were sacrificed.Blood was withdrawn for detection of TNF- α level and arterial blood gases index.And lung tissue slices of the three groups were prepared for observation of pathologic histology changes.Results:TNF- α level in serum of Group Ⅰ and Ⅱ rats was significantly higher than that in Group Ⅲ(P0.05),while TNF- α level in serum of Group Ⅱ was significantly lower in Group Ⅰ(P0.05).PaCO_2 level was significantly higher(P0.05),while PaO_2 was significantly lower(P0.05) in Group Ⅰ and Ⅱ rats than those in Group Ⅲ.PaCO_2 was significantly lower(P0.05) and PaO_2 was significantly higher(P0.05) in Group Ⅱ than those in Group Ⅰ.Histological observation showed diffuse congestion and severe edema of luug tissue,obvious thickening and structure damage of alveolar walls and a large amount of neutrophil infiltration in Group Ⅰ rats.Group Ⅱ rats showed mild edema of lung tissue;only a small portion of alveolar walls showed thickening and only a few of neutrophil infiltration could be observed.The degree of injury was remarkably slighter than that of Group Ⅰ rats.Group Ⅲ rats showed clear lung tissue structure and normal morphology:alveolar walls were uniform and the margin was smooth and few neutrophil could be observed.Conclusions:Captopril can significantly reduce serum TNF- α level,elevate PaO_2 and reduce PaCO_2 in rats with ALI.It has a protective effect on ALI rats.     

In vivo andin vitro experiments on relationships between PGA1 and glucose utilization

Summary Thein vivo andin vitro effects of PGA₁ on glucose utilization were investigated in normal rats and in rats with alloxan-diabetes (50 mg/kg i.v. administered 48 hrs before experiment). The animals were divided into two groups. The first group — which included both normal and diabetic animals — was submitted to an IVGTT after a 12-h fast and during a sodium chloride infusion. The glucose load (0.33 g/kg) was rapidly administered 15 min after starting the infusion. In the second group — which equally included normal and diabetic rats — the same GTT was performed during a sodium chloride infusion in which PGA₁ had been diluted, so that a dose of 0.5 g/kg/min was administered. This dose is devoid of any effect on cardiovascular activity. Forin vitro experiments, glucose utilization was studied in therat diaphragm incubated with insulin (200 μU/ml) and PGA₁ (10 and 100 ng): results demonstrated that PGA₁ enhances the insulin effect on glucose utilization and the enhancement is dose-dependent. The same results were observed also in thein vivo experiments: in normal rats PGA₁ really improves glucose utilization without any interference with insulin secretion from B-cells. On the other hand, PGA₁ has no effect on this utilization in diabetic rats. From our experiments it can therefore be concluded that PGA₁ improves glucose utilization, showing a synergic action with the increased quantity of insulin secreted in response to a glucose load. No effect is noted when insulin secretion from B-cells is reduced or absent.     

Expression of FGF-2 and IGF-1 in diabetic rats with fracture

Objective:To observe the change of fibroblast growth factor-2(FGF-2),insulin-like growth factor-1(IGF—1)in serum and bone callus after fracture in diabetic rats,and to explore molecular biological mechanism of healing of diabetic fracture.Methods:Thirty male SD rats were designed into normal(n=13)and control(n=!5)groups randomly.Venous blood was extracted on the 1st,2nd,4th,6th,8th week after surgery.It was certificated and the serum was obtained.Left lower extremity was observed by X-ray.Bone callus at broken ends was observed under light microscope.Expressions of FGF-2 and 1GF-1 in tissue were detected by immunohistochemistry method,and ELISA was used to detect expression of FGF-2 and IGF-I in serum.Results:The results showed a significant increase in the density and area of newly formed bone in the distraction gaps of normal rats compared to control rats.Increased cell proliferation was also found in the distraction gaps of normal rats versus control rats.There was significant difference in serum levels of FGF-2 and IGF-1 between two groups.Conclusions:The decrease of FGF-2 and IGF-1 both in the serum and in the fracture region is one of the reasons for bad bone healing or delayed union in rats'fracture with diabetes.There are some synergistic effects possibly between FGF-2 and ICF-I.