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Abstract; Aim To explore the effect of icariin (ISO) in mice. Methods C57BL/6 mice were ran- (ICA) on myocardial fibrosis induced by isoproterenol domly divided into control group, ISO group, low-dose (15 mg • kg"1), middle-dose (30 mg • kg"1) and high-dose (60 mg • kg"1) of ICA-treated group and Losartan-treated group ( 9 mg • kg"1 ). The control group was subcutaneously injected with normal saline, and the other groups were subcutaneously injected with ISO (5 mg • kg"1, qd) continuously 14 days to established the myocardial fibrosis model. The ICA-treated groups and Losartan-treated group were simultaneously intragastrically administered of ICA or Losartan, respectively. And the other groups received the same a- mount of double distilled water. The left ventricular e- jection fraction (LVEF) and the left ventricular fraction shortening rate ( LVFS) were evaluated by the small animal ultrasound. The heart mass index (HMI) was calculated. The left ventricular collagen deposition was detected by Masson staining. The protein expressions of a-SMA, MMP-2, MMP-9 and TIMP-1 in the left ventricular tissue were detected by Western blot. Results ICA (30, 60 mg • kg"1) and Losartan could inhibit the decreased LVEF and LVFS, the increased HMI and left ventricular collagen deposition, the up- regulated a-SMA and MMP-9 protein expression, the down-regulated MMP-2 and TIMP-1 protein expression in the left ventricular tissues induced by ISO. Conclusions ICA can improve myocardial fibrosis induced by ISO in mice, and the underlying mechanism may be related to the regulation of the protein expression of a- SMA and MMPs/TIMP-1.
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Aim To explore the effect of miR-152 on proliferation of cardiac fibroblasts ( CFS) in diabetic cardiomyopathy. Methods Diabetic cardiomyopathy model was established in SD rats by STZ injection, and CFS proliferation model was established by high glucose (33. 3 mmol • L ~1). HE and Masson staining were performed in paraformaldehyde fixed myocardium of rats. Western blot determined a-SMA and collagen I protein expression. qPCK detected gene expression of miR-152. MTT assay analyzed the proliferation of cells. Results HE and Masson staining showed the higher level of myocardial collagen in diabetic cardiomyopathy model. Furthermore, the myocardial myo-cytes lined up in disorder. Western blot showed that the expressions of a-SMA and collagen I were up-regulated in the diabetes mellitus ( DM ) group, while the expression of miR-152 was down-regulated. The result of the in vitro experiment showed that a-SMA and collagen I expressions were down-regulated after trans-fected miR-152 mimics. The proliferation of CFS was also down-regulated after transfected miR-152 mimics. Conclusions miR-152 plays an important role in the proliferation of CFS and may ameliorate diabetic cardiomyopathy.
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Objective: To investigate the effect of ethyl acetate extract of Shenbing No. 1 Decoction (EASD) on the expression of TGF-β1 and a-SMA in rats with renal fibrosis. Methods: Totally 50 SD rats were randomly divided into Sham operation group, unilateral ureteral obstruction (UUO) model group, Lotensin treated group (1.67 mg/kg), Shenbing No. 1 Decoction group (18.75 g/kg) and EASD group (300 mg/kg). A rat model of renal fibrosis was induced by unilateral ureteral ligation. The rats were executed after 14 d. The contents of 24 h urinary protein (24hUP), serum blood urea nitrogen (BUN), and serum creatitine (Scr) were tested. Renal tubular interstitial fibrosis was evaluated by HE staining and Masson staining. The protein expression levels of TGF-β1 and a-SMA were observed by immunohistochemical method. Quantitative real-time PCR was adopted to inspect the mRNA expression of a-SMA and TGF-β1. Results: Compared with Sham-operation group, in rats of other groups, the serum levels of BUN and SCr increased (P 0.05). Conclusion: Shenbing No. 1 Decoction and EASD may ameliorate renal interstitial fibrosis by down-regulating the expression levels of TGF-β1 and a-SMA.
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Objective To investigate the effect of 15d-PGJ2 on the expression of collagen type,CTGF and a-SMA in the hypertrophic scar in the rabbit ear,and the possibility of hypertrophic scar treated by 15d-PGJ2.Methods 18 New Zealand white rabbits were used to establish a hypertrophic scar model on the rabbit ear.The wounds were established as follows:2 cm × 3 cm wounds with total skin loses on the ventral side,2 wounds for each ear,totally 72 wounds.The wounds were randomly divided into the 15d-PGJ2 treatment group and NS control group.20μl 15d-PGJ2 or NS was injected into the ear scar once a day for 7 days.At 7,14 and 21 days after the injection,12 scars of each group were harvested.The expression of collagen type Ⅰ,CTGF and a-SMA was detected by immunohistochemical method.Results Excessive dermal scars on rabbit ears that were similar to human hypertrophic scar appeared in the two groups.Compared with the NS-treated scars group,the 15d-PGJ2-treated scars appeared to be smaller,softer,flatter and lighter in color.The expression of collagen type Ⅰ,CTGF and a-SMA in the 15d-PGJ2 group was significantly decreased as compared with that in the control group at different time points(P＜0.05).Conclusion 15d-PGJ2,the ligand of PPAR-r,can reduce the expression of collagen type Ⅰ,CTGF and a-SMA of hypertrophic scar in the rabbit ears and plays an important role in the prevention and treatment of hypertrophic scar.It may provide a new approach for the treatment of hypertrophic scar in clinical setting.
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BACKGROUND/AIMS: Liver cirrhosis is an end-stage liver disease. Ito cell is known to have central role in fibrogenes is of liver cirrhosis. But collagen content and Ito cell activity in liver cirr hosis have received little attention. So Ito cell activity and hepatocyte proliferation activity according to collagen content was investigated. WAF-1 and c- met were studied to evaluate the effect of cell cycle. METHODS: We analyzed 56 cases of liver cirrhosis ( viral:41, biliary:11, alcoholic:2, Wilson' s disease:2). Collagen content was measured by spectrophot ometry. Ito cell activity and prolifer ation index was measured by-SMA and Ki- 67 immunohistochemistry. RESULTS: In viral cirrhosis, high collagen group showed increased Ito cell activity compared to low collagen group. There was no difference in hepatocyte prolifer ation activity bet ween high and low collagen group in viral cirrhosis. In biliary cirrhos is, high collagen group showed increased Ito cell activity in septal zones compared to low collagen group. WAF- 1and c- met were negative in most of cases. CONCLUSION: Collagen content of liver cirrhosis is closely related to increment of activated Ito cells . Ito cell activity was prominent in septal zones than in parenchymal areas of viral cirrhosis and that was only significant in septal zones of biliary cirrhosis. There is no correlation bet ween collagen content and hepatocyte proliferation activity.
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Cell Cycle , Collagen , Fibrosis , Hepatic Stellate Cells , Hepatocytes , Immunohistochemistry , Liver Cirrhosis , Liver Cirrhosis, Biliary , Liver Diseases , LiverABSTRACT
BACKGROUND/AIMS: The aim of this study was to evaluate the effect of alpha-interferon (IFN) on liver histology as well as on activation of hepatic stellate cell ( HSC) and trans for ming growth fact or beta-1 (TGF beta-1) expression. We had also investigated the clinical usefulness of TGFbeta-1 and alpha-smooth muscle actin (alpha-SMA) expression in liver tissue for predicting a response to alpha-IFN therapy in chronic hepat it is B. METHODS: We studied the expression of TGFbeta-1 and alpha-SMA in liver biopsys pecimens from 51 chronic hepatitis B pat ients. Using immunohistochemical staining and a semiquant it ative scoring met hod, we also evaluated TGF-beta1 and alpha-SMA expression in liver stellate cells before and after alpha-IFN therapy in liver tissue from rebiopsys pecimen of the 12 chronic hepatitis B pat ients. Recombinant IFN alpha-2b (Intron A) in doses of 6 MU/ d was given to patients intramus cularly three times per week for 6 months (total doses , 432 MU). The patients were divided into two groups according to serum alanine aminotransferase levels as well as HBV- DNA and HBeAg s eroconversion stat e. Histological grading and staging scores were according to modified Histological Activity Index (HAI) grading systems of Ishak (1995). RESULTS: The index of portal inflammation and total scores of HAI grading significantly decreased in biopsies after alpha-IFN treatment, but the scores of fibrosis staging showed no significant change in biopsies after IFN treatment. A significant decrease in alpha-SMA expression, especially in periportal area, was found, but the change of TGFbeta-1 expression was not significant. The immunoreactivity of alpha-SMA was significantly lower in responders than in non-responders, whereas the diffference of immunoreactivity of TGF-beta1 between these two groups was not found. CONCLUSIONS: These findings suggest that alpha-IFN therapy may reduce the necroinflammatory activity in liver tissues of chronic B viral hepatitis and that the degree of alpha-SMA expression before treatment may be employed as a pottent predicting indicator for the therapeutic efficacy of IFN-alpha.