Efficacy and mechanisms of Dingxian pill(定痫丸)combined with valproic acid on pentylenetetrazol-induced chronic epilepsy in rats

OBJECIVE: To investigate the efficacy and mechanisms of Dingxian pill(定痫丸) combined with valproic acid(VPA) on pentylenetetrazol-induced chronical epilepsy in rats.METHODS: A rat model of epilepsy was established by administering pentylenetetrazol(PTZ) water solution(35 mg/kg). Rats were divided into 4 groups, among which three groups were treated with different drugs once a day for 28 d including Dingxian pill(2.4 g/kg), VPA(0.2 g/kg), or a combination of Dingxian pill(2.4 g/kg) and VPA(0.2 g/k...     

Extract of Yokukansan improves anxiety-like behavior and increases serum brain-derived neurotrophic factor in rats with cerebral ischemia combined with amyloid-β42 peptide

OBJECTIVE: To examine the effects of Yokukansan(YKS) extract on two endogenous modulators of anxiety, brain-derived neurotrophic factor(BDNF)and serotonin (5-HT)_(2A) receptors pharmacologically, in the ischemic rat model of dementia.METHODS: The cerebral ischemia(CI) was induced by bilateral occlusion of the vertebral and common carotid arteries(4-vessel occlusion ischemia). The CI was combined with the amyloid-β42 peptide(A42) injected intracerebroventricularly, and referreβdto as CI+Aβ. Anxiety-like behaviors were assessed by elevated plus maze(enclosed arm), light/dark transition test(dark chamber), and open-field test.Wet-dog shakes were induced by the 5-HT_(2A) receptor agonist 2, 5-dimethoxy-4-iodoamphetamine(DOI). The concentration of BDNF in serum was determined by enzyme-linked immuno sorbent assay.RESULTS: CI + Aβ increased anxiety, as demonstrated by the increase of time spent in the enclosed arms and dark chambers, and locomotion in the outer zone of the open field(thigmotaxis). CI + Adecreased the serum concentration of BDNF. YKS reβ-duced the anxiety-like behaviors, suppressed the DOI-induced wet-dog shakes and increased serum BDNF concentrations.CONCLUSION: Our findings suggest that YKS extract improves CI + Aβ-induced anxiety by antagonizing 5-HT_(2A) receptors and increasing BDNF.     

Effects of Shengmai Yin(生脉饮)on pulmonary and cardiac function in coronavirus disease 2019 convalescent patients with cardiopulmonary symptoms:a randomized,double blind,multicenter control trial

OBJECTIVE: To evaluate the efficacy and safety of Shengmai Yin(生脉饮, SMY) on visual analogue scale(VAS) for cardiopulmonary symptoms in coronavirus disease 2019(COVID-19) convalescent patients. METHODS: In this randomized, double blind and multicenter controlled trial, a total of 200 COVID-19 convalescent patients who with cardiopulmonary symptoms were enrolled from three medical centers in Hubei, China. These patients were randomized divided into trial group and the control group, 100 patients i...     

Effect of Zhuyeshigao granule on tumor necrosis factor-α and interleukins serum protein levels in rats with radiation esophagitis

Objective

To investigate the effects of Zhuyeshigao granule (ZSG) on tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-2, IL-6, and IL-8 in rats with radiation esophagitis.

Methods

Fifty Wistar rats were randomly divided into five groups (10 rats in each group): control (without radiation), saline-treated, and low, medium, and high-dose ISG-treated groups. Rats were given normal saline (10 mL/kg) or 1.15, 2.3, or 4.6 g/kg ZSG by intragastric administration once a day for 7 days. A rat model of radiation esophagitis was established by local irradiation of Co60 (490.25 cGy/min, totaling 30 Gy). The administration of ZSG was continued for another 7 days and on the 7th day post-irradiation, inferior vena cava blood was collected. The serum was separated, and TNF-α, IL-1, IL-2, IL-6, and IL-8 protein levels were determined.

Results

Inflammatory response factors were found in the serum of each group. However, levels in ZSG-treated groups were significantly lower than in the saline-treated group (P<0.05).

Conclusion

ZSG may prevent the development of radiation esophagitis, perhaps by inhibiting the generation and release of the inflammatory response factors TNF-α, IL-1, IL-2, IL-6, and IL-8.     

Effect of moxibustion on expressions of HO-1 and MCP-3 protein in colon of rats with Crohn’s disease

Objective

To observe the effect of moxibustion therapy on heme oxygenase-1 (HO-1) and monocyte chemoattractant protein-3 (MCP-3) protein expressions in the colonic mucosa of rats with Crohn’s disease (CD), and to explore the intestinal mucosal immune mechanism of moxibustion therapy in treating CD.

Methods

The CD rat model was established using the internationally accepted Morris method. The rats were randomly divided into a model group, a herbal cake-partitioned moxibustion group, a mild moxibustion group, a cigarette moxibustion group and a hot compress group, which were compared with the normal group. Except the normal group and the model group, rats in the other groups accepted different moxibustion therapies on bilateral Tianshu (ST 25). Hematoxylin-eosin (HE) staining was conducted and the pathological changes of the colon were observed under light microscope; the expressions of HO-1 and MCP-3 protein in rat’s colonic mucosa were determined by immunohisto-chemistry.

Results

Compared with the normal group, rats in the model group showed mucosal defect, villus destruction or loss, submucosal congestion and edema, glandular destruction or disappearance, reduced goblet cells, ulcer formation, significantly increased positive target area and positive target integral optical density of HO-1 and MCP-3 protein expression (all P<0.01). After treatment, compared with the model group, colonic mucosa was significantly improved in the herbal cake-partitioned moxibustion group and the mild moxibustion group, which mainly showed that the intestinal glands were arranged regularly, ulcer surfaces were covered by the neoformative epitheliums, or intestinal ulcers were replaced by the nascent granulation tissue, and submucosal edema was alleviated, with a small amount of inflammatory cell infiltration. The total areas and the integral optical densities of the positive targets for rat’s colonic mucosa HO-1 and MCP-3 protein expressions were decreased (all P<0.01). Compared with the cigarette moxibustion group and the hot compress group, the total areas and the integral optical densities of the positive targets for rat’s colonic mucosa HO-1 and MCP-3 protein expressions were significantly decreased (all P<0.01) in the herbal cake-partitioned moxibustion group and the mild moxibustion group.

Conclusion

Herbal cake-partitioned moxibustion and mild moxibustion can significantly improve the inflammatory response of colonic mucosa in CD rats. It can down-regulate the expressions of HO-1 and MCP-3 proteins in the colonic mucosa of CD rats, which may be one of the mechanism in intestinal mucosal immunity caused by moxibustion therapy.

     

Effect of acupuncture plus thunder-fire moxibustion on MMP-3, TIMP-1 and TGF-β1 in rats with knee osteoarthritis

Objective

To observe the effect of acupuncture plus thunder-fire moxibustion on the expressions of matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1) and transforming growth factor-β1 (TGF-β1) in cartilage of knee osteoarthritis (KOA) rats, and to explore the mechanism of acupuncture plus thunder-fire moxibustion in the treatment of KOA.

Methods

Thirty Sprague-Dawley (SD) rats were randomly divided into a blank control group, a model group and an acupuncture-moxibustion group by random digits table, 10 rats in each group. Rats in the model group and the acupuncture-moxibustion group were injected with papain in the right posterior knee joint to prepare the models. The levels of MMP-3 and TIMP-1 in rat synovium of each group were measured by enzyme-linked immunosorbent assay (ELISA) after 2 weeks of treatment. The level of TGF-β1 was determined by Motic B5 Micro-camera system.

Results

The levels of MMP-3 and TIMP-1 in the cartilage of the model group were significantly higher than those in the blank control group (all P<0.01); the levels of MMP-3 and TIMP-1 in the acupuncture-moxibustion group were lower than those in the model group, and the between-group differences were statistically significant (all P<0.05). The levels of MMP-3 and TIMP-1 in the acupuncture-moxibustion group were higher than those in the blank control group, and the differences were statistically significant (all P<0.05). The level of TGF-β1 in cartilage tissues of the model group was significantly lower than that in the blank control group (P<0.01); the level of TGF-β1 in the acupuncture-moxibustion group was higher than that in the model group (P<0.05), but it was lower than that in the blank control group, and the between-group difference was statistically significant (P<0.05).

Conclusion

Acupuncture plus thunder-fire moxibustion can effectively recover the abnormal expressions of MMP-3 and TIMP-1 in KOA model rats and somewhat up-regulate TGF-β1, which may be one of its mechanisms of acupuncture plus thunder-fire for KOA.

     

Effect of electroacupuncture on urodynamics,PACAP-38 and PAC1R of spinal cord in rats with neurogenic bladder✰

Objective

To investigate the effect and mechanism of electroacupuncture (EA) in the intervention of neurogenic bladder (NB) caused by suprasacral spinal cord injury (SCI).

The expression change of β-arrestins in fibroblast-like synoviocytes from rats with collagen-induced arthritis and the effect of total glucosides of paeony

Aim of the study

To investigate the expression of β-arrestins in fibroblast-like synoviocytes (FLS) from collagen-induced arthritis (CIA) rats and the effect of total glucosides of paeony (TGP).

Materials and methods

TGP and glucosides of tripterygium wilfordii (GTW) were intragastriclly administrated to collagen-induced arthritis (CIA) rats after immunization. The secondary inflammatory reaction was evaluated by hind paw swelling, polyarthritis index and histopathological changes. Antibodies to type II collagen (CII) were determined by enzyme-linked immunosorbent assay (ELISA). Synoviocyte proliferations were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The expression of β-arrestins in synoviocytes from CIA rats was measured by western blot.

Results

The administration of TGP (25, 50, 100 mg/kg) depressed hind paw swelling and decreased the arthritis scores of CIA rats. TGP improved the pathologic manifestations of CIA. Serum anti-CII antibodies level increased significantly in CIA rats, while TGP had no effect on it. Fibroblast-like synoviocytes (FLS) proliferation was inhibited by TGP (50, 100 mg/kg). On d14, d28 after immunization, β-arrestins expression greatly up-regulated in synoviocytes from CIA rats and then returned to baseline levels on d42 after immunization. TGP (50, 100 mg/kg) significantly reduced the expression of β-arrestins.

Conclusion

An inflammatory process in vivo induces an up-regulation of β-arrestins in synoviocytes from CIA rats while TGP can inhibit this change, which might be one of the important mechanisms for TGP to produce a marked therapeutic effect on RA.     

Moxibustion improves experimental colitis in rats with Crohn’s disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor

ObjectiveThis study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn’s disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR).MethodsSprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway.ResultsMild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon.ConclusionMild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation.Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn’s disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194–204.     

Regulation of signaling molecules associated with insulin action, insulin secretion and pancreatic β-cell mass in the hypoglycemic effects of Korean red ginseng in Goto-Kakizaki rats

Ethnopharmacological relevance

Korean red ginseng (KRG) has long history as herbal remedy for antidiabetic effect.

Aim of the study

To study molecular mechanisms by which KRG ameliorates diabetes mellitus, we investigated whether the supplementation with the aqueous extract of KRG as a dietary admixture (1%, w/w) regulates the expressions of signaling molecules that are associated with insulin action, insulin secretion and pancreatic β-cell mass in spontaneously diabetic Goto-Kakizaki (GK) rats.

Methods

An aqueous extract of KRG was supplemented for the estimated dosage to be 0.2 g/kg rat/day beginning at 5 weeks of age for 12 weeks in male GK rats. Plasma glucose levels were measured every 4 weeks. The expressions of signaling molecules that are associated with insulin action, insulin secretion and β-cell mass in tissues were determined by Western blotting.

Results

The 12-week supplementation with KRG significantly (P<0.05) decreased blood glucose compared to control. It up-regulated the expression of glucose transporter (GLUT) 4 in adipose tissue, and down-regulated the expression of protein tyrosine phosphatases (PTP)-1B in adipose tissue and skeletal muscle. It also up-regulated the expression of insulin and down-regulated the expression of uncoupling protein (UCP) 2, Bax and poly (ADP-ribose) polymerase (PARP) in pancreas.

Conclusions

These results suggest that GLUT4, PTP-1B, insulin, UCP2, Bax and PARP may be the primary targets of KRG that result in increase in insulin action and in insulin secretion, and decrease in β-cell mass, and that cause the normalization in glucose homeostasis.     

Effects of electroacupuncture at lower he-sea points on interleukin-1β and high mobility group box 1 in model rats with ulcerative colitis

ObjectiveTo comparatively observe the effect of electroacupuncture at digestive system-related lower he-sea points on the expressions of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) of colon tissues and high mobility group box 1 protein (HMGB 1) of ulcerative colitis (UC) model rats, and to explore whether there is relative specificity of electroacupuncture at Shàngjùxū (

ST 37), one of lower he-sea points of large intestine, in treatment of bowel diseases.MethodA total of 60 SD rats were randomly divided into control group, model group, ST 37 group, Zúsānlľ (

ST 36) group, Xiàjùxū (

ST 39) group and Yánglíngquán (

GB 34) group. There were ten rats in each group; five were males, and five were females. UC models were established by clysis with 2, 4, 6-trinitrobenzene sulfonic acid/alcohol solution. After modeling, treatment was conducted for ten days, specimens were collected, colonic ulcers and inflammation were inspected visually and scored. The content of serum IL-1β and the expressions of TNF-α and HMGB 1 in colon were detected through ELISA.Results

Compared with control group, the scores of colonic ulcers and inflammation, the content of serum IL-1β and the expressions of TNF-α (except ST 37 group) and HMGB 1 were all higher (P<0.05, P<0.01);

compared with model group, the scores of colonic ulcers in ST 36 group and ST 37 group were lower obviously (P<0.05, P<0.01); the expressions of IL-1β, TNF-α and HMGB 1 in the four treatment groups were lower obviously (P<0.01);

compared with ST 37 group, the expressions of IL-1β, TNF-α and HMGB 1 in other three treatment groups were higher obviously (P<0.05, P<0.01); and the scores of colonic ulcers in ST 39 group and GB 34 group were higher obviously (P<0.05).Conclusion

The score of colonic ulcers can be reduced through electroacupuncture at ST 37, ST 36, ST 39 and GB 34, which can also reduce the content of serum IL-1β and the expressions of TNF-α and HMGB 1, and effectively inhibit inflammatory response of colon caused by UC;

the effect trend of the four acupoints in treatment of UC is: ST 37>ST 36>ST 39>GB 34, and electroacupuncture at ST 37 has the best effect with relative specificity.     

Acupuncture at Nèiguān ( PC 6) in combination with respiratory reinforcing and reducing method for 38 cases of cardiac neurosis

ObjectiveTo observe the clinical effect of acupuncture at Nèiguān (

PC 6) in combination with respiratory reinforcing and reducing method for treatment of cardiac neurosis.MethodsThirty-eight patients with cardiac neurosis were selected for treatment through acupuncture at PC 6 in combination with respiratory reinforcing and reducing method. With twice per day, treated for 6 days per week, and 4 weeks as one course, the therapeutic effect was assessed after one course.ResultsTwenty-one cases were cured, 15 cases were remarkably improved, and 2 cases were failed. The total effective rate was 94.7%.ConclusionsAcupuncture at PC 6 in combination with respiratory reinforcing and reducing method is effective in treatment of cardiac neurosis.     

Effect of “three-acupoint and five-needling method” on the expression level of p-ERK 1/2 protein in lung tissue of rats with allergic bronchial asthma

Objective

To explore the effect of “three-acupoint and five-needling method” on the expression level of p-ERK 1/2 protein in lung tissue of rats with allergic bronchial asthma.

Morphologic and morphometric analyses of acetic acid-induced colitis in rats after treatment with enemas from Myracrodruon urundeuva Fr. All. (Aroeira do Sertão)

The present work showed the effects of Myracrodruon urundeuva Fr. All., popularly known as 'aroeira' (AE), in the form of enemas prepared from the stem bark, on several morphologic and morphometric parameters after acetic acid-induced colitis in rats. Enemas from 5-ASA were used as standard while the vehicle, carboxymethylcellulose, was used as a control. The results of the morphological evaluation showed that on day 1 acetic acid produced significantly more necrosis in the groups treated with AE (10% and 20%) or 5-ASA than the controls. However, on day 60, there were more caliciform and absorptive cells in the treated groups compared with the controls. A significantly higher number of eosinophil and mononuclear cells and also collagen deposition in the controls compared with the treated groups were observed on day 60. However, a higher number of polymorphonuclear cells was detected on day 60 only in the AE treated group but not in the 5-ASA group. These data indicate that animals treated with AE or 5-ASA showed complete epithelial tissue regeneration, while in the controls chronic inflammatory exudate persisted and tissue regeneration occurred through fibrosis.     

Interaction of five anthraquinones from rhubarb with human organic anion transporter 1 (SLC22A6) and 3 (SLC22A8) and drug–drug interaction in rats

Ethnopharmacological relevance

Rhubarb is a well-known traditional Chinese medicine and has been used in China for thousands of years. Anthraquinone derivatives including rhein, emodin, aloe-emodin, chrysophanol and physcion are the important components in rhubarb.

Materials and methods

Here we studied the interaction of five anthraquinone derivatives with human renal organic anion transporter 1 (hOAT1) and hOAT3 stably expressed in cells, and interaction of rhein or rhubarb extract (RE) with furosemide (FS, substrate of OATs) in rats.

Results

Uptake of 6-carboxyl fluorescein via hOAT1 and fluorescein via hOAT3 were markedly inhibited by rhein, emodin and aloe-emodin, and slightly inhibited by chrysophanol and physcion. The estimated IC₅₀ values for rhein, emodin, aloe-emodin and probenecid (typical inhibitor of hOAT1 and hOAT3) were 0.23, 0.61, 2.29 and 18.34 μM for hOAT1, and 0.08, 1.22, 5.37 and 5.83 μM for hOAT3, respectively. Furthermore, the data from the cellular accumulation assay indicated that these five compounds were not substrates of hOAT1 or hOAT3. Pharmacokinetic interaction between rhein and FS in rats showed that area under the curve (AUC_0–t) for FS was increased by 65% when coadministrated with rhein. RE was also used to interact with FS in rats and results showed that AUC_0–t of FS was increased by 32% and by 52% when coadministrated with single-dose or multiple-dose of RE, respectively.

Conclusions

These findings suggested that five anthraquinones inhibited hOAT1 and hOAT3, but these compounds were not transported by hOAT1 or hOAT3. Furthermore, rhein or RE, might cause drug–drug interaction when coadministrated with substrates of OAT1 or OAT3 in vivo.     

Regulatory effects of herbal cake-partitioned moxibustion on the expressions of IL-17, IL-23 and their mRNAs in the colon of rats with Crohn’s disease

Objective

To observe the regulatory effects of herbal cake-partitioned moxibustion on Crohn's disease (CD) rat’s colon inflammatory cytokine interleukin-17 (IL-17), IL-23 and their mRNAs, and to investigate the action mechanism of moxibustion in treating CD.

Methods

Forty SPF grade Sprague-Dauley (SD) male rats were randomly divided into a normal group, a model group, an herbal cake-partitioned moxibustion group and a Western medicine group, with 10 rats in each group. Except the normal group, rats in the other three groups were used to make CD model by giving an enema in colon with Trinitro-benzene-sulfonic acid (TNBS). When the models were successful made, rats in the model group had no therapeutic intervention; rats in the herbal cake-partitioned moxibustion group were subjected to herbal cake-partitioned moxibustion treatment at bilateral Tianshu (ST 25) plus Qihai (CV 6); and rats in the Western medicine group were given oral Mesalazine. After treatment, the histopathological changes and inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were observed in descending colon by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-PCR) methods.

Results

Colon tissues of TNBS enema rat models showed cracks-like ulcers accompanied by mucous layer inflammation, granulomas, and inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were all higher than those in the normal group (P<0.01); after intervention, colon tissue cracks-like ulcers and inflammation degree reduced, inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were all significantly decreased (P<0.01) in the herbal cake-partitioned moxibustion group and the Western medicine group.

Conclusion

Herbal cake-partitioned moxibustion may improve colon tissue ulcers and relieve intestinal inflammation by down-regulation of IL-17, IL-23 and their mRNAs expressions in CD model rats’ colonic mucosa.

     

Changes in nitric oxide,angiotensin Ⅱ, angiopoietin-like protein 4 mRNA,neuregulin 1 mRNA,and platelet endothelial cell adhesion molecule-1 in rats with acute blood stasis induced by high-molecular-weight dextran

OBJECTIVE: To investigate the influence of acute blood stasis on nitric oxide(NO), angiotensin Ⅱ(Ang Ⅱ), angiopoietin-like protein 4(ANGPTL4)m RNA, neuregulin 1(NRG-1) m RNA, and platelet endothelial cell adhesion molecule-1(PECAM-1) in rats with stasis induced by high-molecular-weight dextran(HMWD).METHODS: Seventy-five Sprague Dawley rats were divided randomly into five groups(n = 15 in each group): control group, immediate group, 1 h group,3 h group, and 6 h group. A model of acute blood stasis was established via injection of HMWD into the tail vein. After performing electrocardiogram at the predetermined times according to the grouping, we collected blood and cardiac samples for hematoxylin-eosin(HE) staining and histopathological examination via transmission electron microscopy. Enzyme-linked immunosorbent assay was used to detect plasma levels of NO, AngⅡ, and fibrinogen. Real-time polymerase chain reaction was used to detect the expression of ANGPTL4 m RNA and NRG-1 m RNA. Immunohistochemical methods were used to detect PECAM-1 protein expression.RESULTS: The rat model of blood stasis showed blood retention in the capillary lumens. The ST segment showed gradual elevation, and was still elevated at 3 and 6 h after induction of blood stasis.HE staining showed myocardial cell necrosis and dissolution after modeling, along with basement membrane rupture and mitochondrial structural damage. Transmission electron microscopy showed endothelial cell swelling and an increase in absorption vesicles immediately after modeling. Endothelial cell apoptosis was increased at 3 and 6 h after modeling. Cardiac muscle fibers were disordered and intercalated discs were blurred immediately after modeling. There were massive numbers of dissolved cardiac muscle fibers, ruptured basement membranes, and mitochondrial structural damage at 3 and 6 h after modeling. NO plasma concentration was significantly reduced immediately and 1 h after modeling, while it was increased at 3 and 6 h.AngⅡ plasma concentration was decreased immediately after modeling, but increased at 1, 3, and6 h. Fibrinogen plasma concentration was significantly increased at immediate, 1, 3, and 6 h after modeling. PECAM-1 protein expression was obviously increased immediately after modeling, at 1, 6 h was found mild augment. Expression of Ang PTL4 m RNA was increased at immediate, 1, 3, and 6 h after modeling, and was found further augment at 3,and 6 h. Expression of NRG-1 m RNA was increased at immediate, 1, 3, and 6 h after modeling, and the strongest expression was at 1 h.CONCLUSION: The pathological manifestation of acute blood stasis is characterized by microvascular blood retention. Prolonged blood stasis leads to worsening endothelial cell and cardiomyocyte damage, along with imbalances in the expression of vasomotor factors and increased vascular tone.The pathological damage caused by blood stasis also promotes the expression of cell protection factors.     

Effect of Sini decoction on angiotensin Ⅱ, transforming growth factor β_1 and connective tissue growth factor in rats with myocardial fibrosis-induced banding of the abdominal aorta

OBJECTIVE: To investigate the effect of Sini decoction on rats with myocardial fibrosis induced by banding the abdominal aorta, and explore the mechanism underlying its actions on angiotensin Ⅱ(Ang Ⅱ), transforming growth factor-β_1(TGF-β_1)and connective tissue growth factor(CTGF).METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into sham operation, model, Captopril, and Sini decoction groups. The models were established by the partial banding of the abdominal aorta according to Doering's method.Eight weeks later, heart weight indexes were calculated; hemodynamic changes of the hearts were tested; changes in myocardial tissue morphology were observed by Masson staining; and myocardial collagen volume fraction was calculated. Enzyme-linked immunosorbent assay was used to measure the concentration of Ang Ⅱ in serum. The expression of TGF-β_1 and CTGF were determined by immunohistochemistry and Western blotting.RESULTS: Compared with the sham operation group, the heart weight index, collagen volume fraction of the myocardium, serum levels of Ang Ⅱ,and the expression of myocardial TGF-β_1 and CTGF in the model group were significantly increased(P 0.05). Compared with the model group, the heart weight index, collagen volume fraction of the myocardium, serum levels of Ang Ⅱ, and the expression of myocardial TGF-β_1 and CTGF in all treatment groups were significantly reduced(P 0.05).CONCLUSION: Sini decoction reduced AngⅡ level and inhibited the expression of myocardial TGF-β_1 and CTGF, which may explain the mechanism of its protective effect on myocardium with fibrosis.