Protective effect of diallyl trisulfide on liver in rats with sepsis and the mechanism

The protective effects of diallyl trisulfide on liver were examined in rats with sepsis. Sepsis was reproduced in rats by cecum ligation and puncture (CLP). Fifty-six male Wistar rats were randomly divided into sham-operated group (group S, n=8), sepsis model group (group C, n=24), diallyl trisulfide (DATS)-treated group (group D, n=24). Animals in groups C and D were further divided into three subgroups according to different observation time points, with 8 rats in each sub-group.Rats in group D and C were intravenously injected with normal saline or DATS respectively at a dose of 20 mg/kg after the establishment of sepsis model. Eight rats in groups C and D were sacrificed at 3, 6 and 24 h post-CLP and their livers were harvested for detection of interleukin (IL)-1 receptor associated kinase-4 (IRAK-4), nuclear factor-κB (NF-κB), c-fos, c-jun, malondialdehydethhe (MDA) and superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α) and for pathological examination. The results showed that the levels of serum IRAK-4, NF-κB and TNF-α in hepatic tissues were higher in group C than group S (control group) (P<0.05). After DATS treatment, the levels of IRAK-4 and NF-κB in the hepatic tissues and serum TNF-α in group D were lower than those in group C (P<0.05). The levels of c-fos and c-jun and MDA in the hepatic tissues were higher in group C than in group S (P<0.05). After DATS treatment, the levels of c-fos and c-jun and MDA in the hepatic tissues were significantly lower in group D than in group C (P<0.05). When compared with group S group, concentration of SOD in the hepatic tissues in group C was significantly lower (P<0.05). After DATS treatment, the concentration of SOD in the hepatic tissues was higher in group D than in group C (P<0.05). These findings suggested that treatment with DATS could ameliorate sepsis-induced liver injury in rats. The protective effect might be related to its ability to inhibit the signal pathway of IRAK-4 and NF-κB, thereby decreasing the production o     

Huoxin Pill (活心丸) Attenuates Cardiac Fibrosis by Suppressing TGF-β 1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats

Objective: To evaluate the effects of Huoxin Pill (活心丸, HXP) on cardiac fibrosis and heart failure (HF) in isoproterenol (ISO)-induced HF rats. Methods: Thirty Wistar rats were randomly divided into 5 groups including control, HF, isosorbide mononitrate (ISMN), HXP low (HXP-L), and HXP high (HXP-H) groups (n=6 for each group) according to the complete randomization method. Rats were pretreated with ISMN (5 mg/kg daily), low concentration of HXP (10 mg/kg daily) or high concentration of HXP (30 mg/kg daily) or equal volume of saline by intragastric administration for 1 week, followed by intraperitoneal injection of ISO (10 mg/kg, 14 days), and continually intragastric administrated with above medicines or saline for additional 6 weeks. The effects of HXP treatment on the cardiac function, heart weight index (HWI), pathological changes, and collagen content were further assessed. Moreover, the role of HXP on activation of transforming growth factor-β 1 (TGF-β 1)/Smads pathway was further explored using immunohistochemistry (IHC) and Western blot assay. Results: HXP treatment significantly alleviated the decrease of ejection fraction (EF) and fractional shortening (FS), while decreased the elevation of left ventricular end-systolic volume (LVESV) in ISO-induced HF rats (P<0.05). Moreover, HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB (CK-MB, P<0.05), as well as pathological changes in ISO-induced HF rats. Further determination indicated that HXP treatment alleviated the elevation of collagen Ⅰ and collagen Ⅲ protein expression in cardiac tissues of ISO-induced HF rats. Furthermore, HXP treatment significantly down-regulated the increase of TGF-β 1 and p-Smad2/3 protein expression in cardiac tissues of HF rats (P<0.05), while did not affect the expression of total Smad2/3. Conclusions: HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-β 1/Smad2/3 pathway.     

Effects of Shenfu Injection (参附注射液) on Inflammatory Response during Post-Resuscitation Myocardial Dysfunction after Cardiac Arrest in Swine

Objective: To investigate whether Shenfu Injection (SFI, 参附注射液) can alleviate post-resuscitation myocardial dysfunction by inhibiting the inflammatory response. Methods: After 8 min of ventricular fibrillation and 2 min of basic life support, 24 pigs were randomly divided into 3 groups (n=8), which were given intravenous bolus injections of SFI (1.0 mL/kg), epinephrine (EP, 0.02 mg/kg) and normal saline (SA), respectively. The animals were sacrificed at 24 h after restoration of spontaneous circulation (ROSC), and serum interleuking-6 (IL-6) and tumor necrosis factor-α (TNF-α ) levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κ B) mRNAs and proteins were determined by RT-PCR and Western blot, respectively. Results: Compared with the EP and the SA groups, the ultrastructure of myocardial cells were slightly damaged and the systolic function of the left ventricle was markedly improved in the SFI group at 24 h after ROSC (P<0.05). In addition, compared with the EP and SA groups, the SFI group also showed significantly reduced levels of serum IL-6 and TNF-α , protein and mRNA levels of myocardial NF-κ B and TLR4 (P<0.05). Conclusions: Activation of TLR4/NF-κ B signaling pathway may be involved in the pathological mechanisms of post-resuscitation myocardial dysfunction. SFI may block NF-κ B-mediated inflammatory response by reducing the activity of NF-κ B and the level of TNF-α , thus playing a protective role in post-resuscitation myocardial dysfunction.     

Pioglitazone ameliorates experimental nonalcoholic steatohepatitis by regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats

Background Pioglitazone is effective in nonalcoholic steatohepatitis (NASH), but the mechanism of action is not completely understood. This study was designed to investigate the impact of pioglitazone on hepatic nuclear factor-kappa B (NF-κB) and cyclooxygenases-2 (COX-2) expressions in NASH rats. Methods Thirty Sprague-Dawley male rats were randomly assigned to a control group (n=10), NASH group (n=10) and pioglitazone treatment group (n=10). Liver tissues were processed for histology by HE and Masson stained. Biochemical parameters of antioxidant enzyme activities, tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2) in the serum and hepatic samples were measured. The mRNA and protein expressions of peroxisome proliferator-activated receptor gamma (PPARγ), NF-κB and COX-2 were determined by real-time polymerase chain reaction, Western blotting and immunohistochemistry, respectively. Results There were severe steatosis, moderate inflammatory cellular infiltration and fibrosis in the livers of the NASH models. After treatment, steatosis, inflammation and fibrosis were significantly improved compared with the NASH group (χ2＝20.40, P＜0.001; χ2＝20.17, P＜0.001; χ2＝13.98, P=0.002). The serum and hepatic levels of total anti-oxidation competence (T-AOC), superoxide dismutase (SOD), catalase(CAT), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) in the NASH group were conspicuous disordered than those indicators in the control group. In the NASH group, the levels of serum TNF-α and PGE2 were significantly increased compared with the control group. Immunohistochemistry showed expressions of NF-κB and COX-2 in livers were significantly elevated, but PPARγ was decreased in the NASH group. Real-time PCR and Western blotting revealed mRNA and protein expressions of COX-2 were increased in the NASH group compared with the control group (0.57±0.08 vs 2.83±0.24; 0.38±0.03 vs 1.00±0.03, P＜0.001 and P=0.004, respectively). After pioglitazone intervention, all of those indicators markedly improved(P＜0.05 or P＜0.01 ). Conclusion Suppressing hepatic NF-κB and COX-2 expression, at least in part, is one of the possible therapeutic mechanisms of pioglitazone in NASH rats.     

Effect of Soothing Gan (Liver) and Invigorating Pi (Spleen) Recipes on TLR4-p38 MAPK Pathway in Kupffer Cells of Non-alcoholic Steatohepatitis Rats

Objective: To investigate the mechanism of inflammatory-mediated toll-like receptor 4(TLR4)-p38 mitogen-activated protein kinase(p38 MAPK) pathway in Kupffer cells(KCs) of non-alcoholic steatohepatitis(NASH) rats and the intervention effect of soothing Gan(Liver) and invigorating Pi(Spleen) recipes on this pathway. Methods: After 1 week of acclimatization, 120 Sprague-Dawley male rats were randomly divided into 8 groups using a random number table(n=15 per group): normal group, model group, low-dose Chaihu Shugan Powder(柴胡疏肝散, CHSG) group(3.2 g/kg), high-dose CHSG group(9.6 g/kg), low-dose Shenling Baizhu Powder(参苓白术散, SLBZ) group(10 g/kg), high-dose SLBZ(30 g/kg) group, and low-and highdose integrated recipe(L-IR, H-IR) groups. All rats in the model and treatment groups were fed with a high-fat diet(HFD). The treatments were administrated by gastrogavage once daily and lasted for 26 weeks. The liver tissues were detected with hematoxylin-eosin(HE) and oil red O staining. Levels of liver lipids, serum lipids and transaminases were measured. KCs were isolated from the livers of rats to evaluate the mRNA expressions of TLR4 and p38 MAPK by real-time fluorescence quantitative polymerase chain reaction, and proteins expressions of TLR4, p-p38 MAPK and p38 MAPK by Western blot. Levels of inflammatory cytokines including tumor necrosis factor α(TNF-α), interleukin(IL)-1 and IL-6 in KCs were measured by enzyme-linked immunosorbent assay. Results: After 26 weeks of HFD feeding, HE and oil red O staining showed that the NASH model rats successfully reproduced typical pathogenesis and histopathological features. Compared with the normal group, the model group exhibited significant increases in body weight, liver weight, liver index, serum levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol, and aspartate aminotransferase as well as TC and TG levels in liver tissues, and significant decrease in serum level of high-density lipoprotein cholesterol(P0.05 or P0.01), while those indices were significantly ameliorated in the H-IR group(P0.05 or P0.01). Higher levels of TNF-α, IL-1 and IL-6 in KCs were observed in the model group compared with the normal group(P0.01). Significant decreases in TNF-α, IL-1 and IL-6 were observed in the H-SLBZ, H-IR and L-IR groups compared with the model group(P0.05 or P0.01). The m RNA expressions of TLR4 and p38 MAPK and protein expressions of TLR4, p38 MAPK and p-p38 MAPK in KCs in the model group were significantly higher than the normal group(P0.01), while those expression levels in the L-IR and H-IR groups were significantly lower than the model group(P0.05 or P0.01). Conclusions: Inflammation in KCs might play an important role in the pathogenesis of NASH in rats. The data demonstrated the importance of TLR4-p38 MAPK signaling pathway in KCs for the anti-inflammatory effect of soothing Gan and invigorating Pi recipes.     

Methylprednisolone improves microcirculation in streptozotocin- induced diabetic rats after myocardial ischemia/reperfusion

Background  Methylprednisolone has been demonstrated to decrease inflammation, and it may protect organs from ischemia/reperfusion (I/R) injury. This study aimed to investigate the effects of methylprednisolone on diabetic myocardial I/R injury.

Methods  Forty adult male Sprague-Dawley (SD) rats were randomized into five groups (n=8 in each group) including a sham operation (sham) group, I/R group, diabetic sham operation (DMS) group, diabetic I/R (DM-I/R) group and methylprednisolone intervention (MP+DM-I/R) group. The diabetic model was produced by injection of streptozotocin (STZ). Body weight and blood glucose levels were determined after diabetes was established. Twelve weeks after induction of diabetes, a segmental I/R of the heart was induced by occluding the left anterior descending artery for one hour and then three hours of reperfusion in the I/R, DM-I/R and MP+DM-I/R groups. Blood pressure and electrocar- diogram were continuously recorded during the procedure. IL-1β, IL-6 and TNF-α were measured at certain time points during the surgery. After reperfusion, a microcirculation scan was performed; myocardial biomarkers and tissue structure were utilized to evaluate the reperfusion damage. Intercellular adhesion molecule (ICAM)-1 and NF-κBp65 expression were quantified by immunohistological staining. Total Toll-like receptor 4 (TLR4) and nuclear NF-κBp65 protein were determined by Western blotting.

Results  Twelve weeks after diabetes was established, blood glucose levels were elevated and body weights were lower in diabetic rats. After reperfusion, infarction size was increased, myocardial biomarkers and inflammatory cytokines levels were elevated. Microcirculation perfusion was significantly reduced in the DM-I/R group compared with the I/R group, however it was improved in the MP+DM-I/R group. The expression of NF-κBp65 and ICAM-1 were increased in the DM-I/R group and decreased in the MP+DM-I/R group. Compared with the non-diabetic I/R group, TLR4 and NF-κBp65 protein levels were up-regulated in the DM-I/R group, but down-regulated in the MP+DM-I/R group.

Conclusions  Methylprednisolone improves microcirculation in STZ-induced diabetic rats after myocardial ischemia/reperfusion, which may associate with the suppression of TLR4/NF-κB signaling.

     

Protective Effect of Norcantharidin on Collagen-Induced Arthritis Rats

Objective: To observe the effect of norcantharidin(NCTD) on collagen-induced arthritis(CIA) rats. Methods: Sixty Sprague-Dawley(SD) rats were randomly divided into 6 groups(n=10): normal group, CIA model group(model group), NCTD low-dose group [1.35 mg/(kg·d)], NCTD middle-dose group [2.7 mg/(kg·d)], NCTD high-dose group [5.4 mg/(kg·d)] and methotrexate(MTX) group [1.8 mg/(kg/w)]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin(HE) staining. The serum levels of interleukin(IL) 1β, IL-6, tumor necrosis factor(TNF)-α, vascular endothelial growth factor(VEGF), IL-17 and transform growth factor(TGF) β were detected by enzyme linked immunosorbent assay(ELISA). The mRNA expression of retinoid-related orphan nuclear receptor γ t(ROR γ t) and forkhead box P3(Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction. Results: MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats' ankle joints compared with the model group(P0.05 or P0.01). All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats(P0.05). Only middle-and high-dose of NCTD prominently decreased serum IL-1β and TGF-β levels of CIA rats(P0.05). However, NCTD has no effect on vascular endothelial growth factor(VEGF) level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group(P0.05). The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group(P0.05). Conclusion: NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.     

Fuzheng Huayu Formula (扶正化瘀方) Prevents Rat Renal Interstitial Fibrosis Induced by HgCl2 via Antioxidative Stress and Down-regulation of Nuclear Factor-Kappa B Activity

Objective: To investigate the mechanism of action of Fuzheng Huayu Formula (扶正化瘀方, FZHY) against renal interstitial fibrosis (RIF) relating to oxidative injury and nuclear factor-kappa B (NF-κB) activity. Methods: Thirty-two Sprague-Dawley rats were randomly divided into 3 groups: normal group, model group and FZHY treatment group. The RIF model was induced by oral administration of HgCl2 at a dose of 8 mg/kg body weight once a day for 9 weeks. Meanwhile, rats in FZHY treatment group orally took FZHY at a dose of 4.0 g/kg rat weight for 9 weeks. The content of hydroxyproline (Hyp) and collagen deposition in kidney were observed. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the content of glutathione (GSH) and malondialdehyde (MDA) of kidney were tested. The expressions of inhibitor-κappa B (IκB), phospho-IκB (p-IκB), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-2 (MMP-2) and α-smooth muscle actin (α-SMA) were analyzed by Western blot. α-SMA expression was also observed by immunofluorescent staining. MMP-2 activity was measured by gelatin zymography. NF-κB activation was determined by electrophoretic mobility shift assay. Results: Renal interstitial fibrosis was induced by HgCl2, demonstrated by remarkably increased Hyp contents and excessive collagen deposition in kidney (P<0.01). FZHY significantly inhibited renal interstitial collagen deposition and reduced Hyp content of the HgCl2-treated rats (P<0.01). GSH content decreased obviously, and MDA content increased significantly in HgCl2-treated rats compared with that of normal rats (P<0.01). FZHY significantly increased GSH content and decreased MDA content in the model rats (P<0.01). The expression α-SMA was increased in model rats compared with that of normal rats, FZHY significantly decreased its expression (P<0.01). The expressions of p-IκB and TNF-α and MMP-2, MMP-2 activity, and NF-κB activation were increased in model group compared with that in normal group (P<0.01), FZHY significantly decreased NF-κB activation, MMP-2 activity and p-IκB and TNF-α expressions (P<0.01). Conclusions: FZHY could protect kidney from oxidative injury intoxicated by HgCl2, and antagonized oxidative stress-stimulated NF-κB activity through inhibition of IκB phosphorylation in the interstitial fibrotic kidney, these effects importantly contributed to FZHY action mechanism against renal interstitial fibrosis.     

Protective effect and mechanism of sodium tanshinone II A sulfonate on microcirculatory disturbance of small intestine in rats with sepsis

To explore the protective effect of sodium tanshinone ⅡA sulfonate(STS) on microcirculatory disturbance of small intestine in rats with sepsis,and the possible mechanism,a rat model of sepsis was induced by cecal ligation and puncture(CLP).Rats were randomly divided into 3 groups:sham operated group(S),sepsis group(CLP) and STS treatment group(STS).STS(1 mg/kg) was slowly injected through the right external jugular vein after CLP.The histopathologic changes in the intestinal tissue and changes of mesenteric microcirculation were observed.The levels of tumor necrosis factor-α(TNF-α) in the intestinal tissue were determined by using enzyme-linked immunoabsorbent assay(ELISA).The expression of intercellular adhesion molecule-1(ICAM-1) in the intestinal tissue was detected by using immunohistochemisty and Western blot,that of nuclear factor κB(NF-κB) and tissue factor(TF) by using Western blot,and the levels of NF-κB mRNA expression by using RT-PCR respectively.The microcirculatory disturbance of the intestine was aggravated after CLP.The injury of the intestinal tissues was obviously aggravated in CLP group as compared with S group.The expression levels of NF-κB p65,ICAM-1,TF and TNF-α were upregulaed after CLP(P<0.01).STS post-treatment could ameliorate the microcirculatory disturbance,attenuate the injury of the intestinal tissues induced by CLP,and decrease the levels of NF-κB,ICAM-1,TF and TNF-α(P<0.01).It is suggested that STS can ameliorate the microcirculatory disturbance of the small intestine in rats with sepsis,and the mechanism may be associated with the inhibition of inflammatory responses and amelioration of coagulation abnormality.     

Fuzheng Huayu Formula(扶正化瘀方) Prevents Rat Renal Interstitial Fibrosis Induced by HgCl_2 via Antioxidative Stress and Down-regulation of Nuclear Factor-Kappa B Activity

Objective:To investigate the mechanism of action of Fuzheng Huayu Formula(扶正化瘀方,FZHY)against renal interstitial fibrosis(RIF)relating to oxidative injury and nuclear factor-kappa B(NF-κB)activity.Methods:Thirty-two Sprague-Dawley rats were randomly divided into 3 groups:normal group,model group and FZHY treatment group.The RIF model was induced by oral administration of HgC l2 at a dose of 8 mg/kg body weight once a day for 9 weeks.Meanwhile,rats in FZHY treatment group orally took FZHY at a dose of4.0 g/kg rat weight for 9 weeks.The content of hydroxyproline(Hyp)and collagen deposition in kidney were observed.The activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),the content of glutathione(GSH)and malondialdehyde(MDA)of kidney were tested.The expressions of inhibitor-κappa B(IκB),phospho-IκB(p-IκB),tumor necrosis factor-α(TNF-α),matrix metalloproteinase-2(MMP-2)andα-smooth muscle actin(α-SMA)were analyzed by Western blot.α-SMA expression was also observed by immunofluorescent staining.MMP-2 activity was measured by gelatin zymography.NF-κB activation was determined by electrophoretic mobility shift assay.Results:Renal interstitial fibrosis was induced by Hg Cl2,demonstrated by remarkably increased Hyp contents and excessive collagen deposition in kidney(P0.01).FZHY significantly inhibited renal interstitial collagen deposition and reduced Hyp content of the Hg Cl2-treated rats(P0.01).GSH content decreased obviously,and MDA content increased significantly in HgC l2-treated rats compared with that of normal rats(P0.01).FZHY significantly increased GSH content and decreased MDA content in the model rats(P0.01).The expressionα-SMA was increased in model rats compared with that of normal rats,FZHY significantly decreased its expression(P0.01).The expressions of p-IκB and TNF-αand MMP-2,MMP-2 activity,and NF-κB activation were increased in model group compared with that in normal group(P0.01),FZHY significantly decreased NF-κB activation,MMP-2 activity and p-IκB and TNF-αexpressions(P0.01).Conclusions:FZHY could protect kidney from oxidative injury intoxicated by Hg Cl2,and antagonized oxidative stress-stimulated NF-κB activity through inhibition of IκB phosphorylation in the interstitial fibrotic kidney,these effects importantly contributed to FZHY action mechanism against renal interstitial fibrosis.     

Effects of Propofol on The mRNA Expression of Toll-like Receptor 4 in BV-2 Cells During Mimic Ischemia-Reperfusion Injury In Vitro

This study investigated the effects of propofol on the mRNA expression of Toll-like receptor-4 (TLR4) in BV-2 cells during mimic ischemia-reperfusion (I/R) injury in vitro. BV-2 cells, a mouse microglia line, were cultured and divided into 4 groups at random: control group (group C), ischemia/reperfusion group (group I/R), low-dose propofol (25 μmol/L) intervention group (group PF25) and high-dose propofol (100 μmol/L) intervention group (group PF100). The mRNA expression of TLR4 and NF-κB was measured by means of RT-PCR. TNF-α levels in the supernatants of BV-2 cells were detected by ELISA. The results showed that the mRNA expression of TLR4 and NF-κB was significantly higher in groups I/R, PF25 and PF100 than in group C (P<0.01). And the TNF-α level in the supernatants was elevated in groups I/R, PF25 and PF100 as compared with that in group C (P<0.01). After pre-treatment with propofol, the mRNA expressions of TLR4 and NF-κB and the TNF-α level were significantly decreased in groups PF25 and PF100 in comparison to those in group I/R (P<0.01). And the decrease in those indicators was more significant in group PF100 than in group PF25 (P<0.01). It was concluded that propofol exerted brain-protecting effects during I/R injury by suppressing the mRNA expressions of TLR4 and NF-κB and deceasing the TNF-α level.     

Telmisartan protects against insulin resistance by attenuating inflammatory response in rats

This study investigated the effects of telmisartan on insulin resistance in high-fat diet-treated rats and the possible mechanism.A total of 40 male Sprague-Dawley rats enrolled in the study were divided into 4 groups at random:ND group(n=10) and HD group(n=10),in which the rats were given a normal chow diet or a high-fat diet for 20 weeks following a one-week adaptation;ND+telmisartan(n=10) group and HD+telmisartan group(n=10),in which the rats were initially administered in the same way as the ND or HD group,and then they were orally gavaged with telmisartan(5 mg/kg daily) additionally for 5 weeks.Related inflammatory factors were measured by ELISA.Monocyte chemotactic protein 1(MCP-1),phosphorylated JNK and IκB-α expressions in both adipose and liver were detected by Western blotting.CRP and angiotensin Ⅱ receptor 1(AT1) mRNA expressions in both adipose and liver were determined by RT-PCR.The results showed that telmisartan administration in vivo reversed insulin resistance as evidenced by a decrease in plasma fasting glucose levels,plasma fasting insulin levels and homeostasis model of assessment-insulin resistance(HOMA-IR).Furthermore,telmisartan administration significantly reduced serum CRP,TNF-α and IL-1β levels,and elevated serum IL-10 levels.It was also found to hamper the high-fat diet-induced increase in CRP mRNA,AT1 mRNA and MCP-1,and decrease in IκB-α in both adipose and liver.It was concluded that telmisartan administration in vivo may improve insulin resistance through attenuated inflammatory response pathways.     

Protective Effect of Hydroxysafflor Yellow A on Inflammatory Injury in Chronic Obstructive Pulmonary Disease Rats

Objective: To investigate the attenuating effect of Hydroxysafflor yellow A(HSYA) on inflammatory injury in chronic obstructive pulmonary disease(COPD). Methods: Rats were randomly assigned to 7 groups according to body weight including normal control group, HSYA blank group(76.8 mg/kg), COPD group, COPD+HSYA(30, 48, 76.8 mg/kg) groups and COPD+dexamethasone(2 mg/kg), 10 in each group. Passive cigarette smoke and intratracheal instil ation of lipopolysaccharides were used to establish a COPD model in rats. Hematoxylin and eosin staining of lung tissue sections was used, real-time polymerase chain reaction(PCR) was used to assay m RNA levels of some cytokines in lung tissues, the cytokines in bronchoalveolar lavage fluid(BALF) were measured by enzyme-linked immunosorbent assay(ELISA), Western blot analysis was used to determine phosphorylated p38 mitogen-activated protein kinase(MAPK) levels in lung tissues, and nuclear factor-κB(NF-κB) p65 protein levels in lung tissues were detected by immunohistochemistry. Results: Lung alveolar septa destruction, alveolus fusion, inflammatory cel infiltration, and bronchiole exudation were observed. These pathological changes were al eviated in the COPD+HSYA group. The m RNA expression of inflammatory factors were significantly increased in lung tissues from COPD rats(all P0.01) and were inhibited by HSYA. Levels of inflammatory cytokines in BALF of COPD rats were significantly increased(all P0.01) which were inhibited by HSYA(all P0.01, 48, 76.8 mg/kg). The levels of p38 MAPK phosphorylation and p65 in lung tissues of COPD rats were significantly increased(al P0.01) and were suppressed by HSYA(all P0.01, 48, 76.8 mg/kg). Conclusions: HSYA could alleviate inflammatory cell infiltration and other pathological changes in the lungs of COPD rats. HSYA could inhibit inflammatory cytokine expression, and increase phosphorylation of p38 MAPK and NF-κB p65 in the lungs of COPD rats. The protective mechanism of HSYA to inhibit COPD inflammation might be by attenuating NF-κB and p38 MAPK signal transduction.     

Immune Intervention Effects of the Induction of Experimental Autoimmune Thyroiditis

To explore immune intervention effects of the combined use of cycloporin A(CsA) and 1,25-dihydroxyvitamin D3[1,25(OH)2D3]at low doses on experimental autoimmune thyroiditis (EAT),porcine thyroglobulin (pTG) was injected into a CBA mouse at the dose of 100μg on day 0 and day 14 to establish the model of EAT.The immune prevention group from day 0 to day 28,and treatment group from day 10 to day 38 were daily administered CsA (10mg/kg) intragastrically and /or 1,25(OH)2D3(0.2μg/kg)ip.After immunized by pTG,the mice were sacrificed on day 28 and day 38 to examine their thyroid gland pathologically,and to check the levels of serum porcine thyroglobulin antibodies (pTGAb),porcine thyromicrosomal antibodies (pTMAb).The incidences of EAT in the immune prevention group and treatment group,with administration of low dose of CsA and 1,25(OH)2D3,were decreased respectively by 44.44% and 37.50%.Those of severe disease in the two groups were decreased respectively by 71.43% and 60.33%.The levels of serum pTGAb and pTMAb in the immune prevention group were lower than those of the positive control group.It was concluded that combined use of CsA and 1,25(OH)2D3 at low doses could effectively prevent EAT with a synergic effect.