褪黑素保护大鼠肝纤维化的机制探讨

目的研究褪黑素保护大鼠肝纤维化的机制。方法用四氯化碳(CCl4)制造大鼠肝纤维化模型,同时予10 mg.kg-1.d-1褪黑素腹腔注射;在造模的第12周末处死大鼠,观察大鼠肝脏活化核转录因子κB(NF-κB)亚单位P65的表达。用α-SMA单抗标记活化的肝脏星状细胞(HSCs),计算其数量,同时测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白蛋白(ALB)水平及ALB与球蛋白(GLO)比值,并进行肝脏病理学评分。结果褪黑素抑制了NF-κB亚单位P65的活化,活化HSCs数量减少,ALT、AST降低,而ALB和ALB/GLO明显提高,肝脏炎症和纤维化显著减轻(P<0.05~0.01)。结论褪黑素通过抑制NF-κB的激活,减轻肝脏炎症,抑制了HSCs活化,使肝纤维化减轻。

A research on the mechanism of melatonin against rat liver fibrosis

Objective To study the mechanism of melatonin against rat liver fibrosis. Methods Rat liver fibrosis model was induced by carbon tetrachloride （ CCI4 ）, and meanwhile treated with melatonin i. p. at the dose of 10mg/kg body weight. The rats were killed at the end of 12th week ,the expression of activated nuclear factor KB（ NF-κB） subunit p65 in rats＇ liver was analyzed. The activated hepatic stellate cells （HSCs）labeled by or-smooth muscle actin （a-SMA）in the liver specimen were counted. The levels of alanine transaminase （ALT）, asparagic acid transaminase（AST） and albumin（ALB） in serum were measured and the ratio of albumin against globulin（GLO） was calculated. Histological examination of rat liver was also measured. Results Melatonin inhibited the activation of NF-κB ,the number of activated HSCs was also significantly decreased, the levels of ALT, AST were decreased, ALB and ALB/ GLO were increased ,＇hepatic inflammation and liver fibrosis were improved obviously （ P 〈 0.05 ）. Conclusion Melatonin inhibited the activation of NF-κB, ameliorated hepatic inflammation, and inhibited the activation of HSCs, iraproved rat liver fibrosis induced by CCI4.