The Rapeutic Effects And Mechanisms Of Curcumin Derivatives On Experimental Rat Hepatic Fibrosis

Objectiv To investigate the therapeutic effects and mechanisms of curcumin derivatives on experimental rat hepatic fibrosis.Methods (1) The model of hepatic fibrosis in experimental rats60male SD rats were divided into four groups (n=15), respectively for the normal group, model group, the curcumin group, curcumin derivatives group. In addition to the normal group the remaining three groups were injected carbon tetrachloride mixture (CCL4:olive oil=2:3) in all rats for limbs medial subcutaneous5ml/kg for the first time and subsequent2ml/kg one week,then were induced for liver fibrosis model.(2) Detection of curcumin derivatives against liver fibrosis and its possible mechanism:From the fifth weeks curcumin derivatives group were given100mg/kg of curcumin derivatives by vein injections, curcumin group’s normal were given curcumin300mg/kg by gavage treatment daily, normal and model groups were given saline0.2ml of each by tail vein injection every day,then were total of6weeks of treatment. after10weeks the treatment were finished, conventional ether anesthesia from rat heart blood for serological markers of liver function and liver fibrosis were tested, and liver tissue were done by hydroxyproline (Hpy) level detection, after Caesarean Section of liver left lobe of the same site,10%neutral buffered formalin conventional were fixed with HE and Sirius red staining for observe changes of liver pathology, while the assessment of liver fibrosis were graded; TGF-β1and α-SMA cytokines were observed by immunohistochemical method and distributed in the rat liver tissue; the level of TGF-β1mRNA was detected by RT-PCR method in the liver tissues; TGF-β1and β-SMA protein levels were analysised by Western blot method in rat liver.Results (1) Compared with index of liver function and liver fibrosis:Compared with model group, curcumin group and curcumin derivatives group can effectively improved liver function, reduced the serum level of liver fibrosis, reduced the liver tissue hydroxyproline (Hpy) content.The results of curcumin derivatives group and the model group of ALT, AST, HA, LN, PCⅢ, Hyp were tested for (220.1±148.2) U/L contrast (513.2±279.6) U/L、(366.7±157.3) U/L contrast (700.5±305.9) U/L、(150.0±26.0) ug/L contrast (292.8±105.6) ug/L、(28.2±4.8) ug/L contrast (48.8±7.1)ug/L、(30.2±3.8) ug/L contrasted (46.3±6.4) ug/L、(293.8±54.3) ug/g contrast (412.8±53.8) ug/g, and both differences were statistically significant (P<0.05);(2) Compared with Pathological picture and pathological grade: Compared with model group, curcumin derivatives could significantly decrease the liver pathological grade (pathological grade of curcumin derivatives group were distributed in grade2while the modle group mainly distributed in grade5,6), hepatic lobule structure of curcumin derivatives group was normal and a small amount of fibrous tissue were proliferated, showing that a small amount of inflammationcell infiltration and fatty were degenerated and vacuolated, fibrosis is not obvious and no false lobular formation, but in the model group,there were obvious lobular architecture of destruction, significantly changed in inflammatory cell infiltration and deranged liver cord, and the fibrous tissue of the portal area is obvious hyperplasia in part of the formation of false lobules. curcumin derivatives group was significantly inhibited fibrosis and improved the organizational structure of the liver pathology than the model group;(3) Detected by immunohistochemical methods, we found that the molecular expression of TGF-β1and α-SMA were significantly reduced after treatment of curcumin derivatives compared with the model group in rat liver.And collagen I was significantly decreased in curcumin derivatives compared with the model group.(4) RT-PCR assay results showed that curcumin derivatives group of TGF-β1mRNA levels was significantly reduced than the model group; by Western blot to detect the expression of TGF-β1and α-SMA protein expression in liver tissue than in model group decreased significantly reduce the difference was statistically significant (P<0.05). Conclusion This study reveals that the curcumin derivatives has a significant effect of anti-liver fibrosis, while reduced the expression of TGF-β1and α-SMA cytokine and inhibited the activation of hepatic stellate cell may be the mechanism of anti-hepatic fibrosis.