安五脂素改善大鼠肝纤维化的效果及机制
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篇名: | 安五脂素改善大鼠肝纤维化的效果及机制 |
TITLE: | The effect and mechanism of anwulignan on improving hepatic fibrosis in rats |
摘要: | 目的 探讨安五脂素改善大鼠肝纤维化的效果及作用机制。方法将50只SD大鼠随机分为正常组,模型组,秋水仙碱片组(0.1mg/kg),安五脂素高、低剂量组(2.8、0.7mg/kg),每组10只。除正常组外,其余各组大鼠均腹腔注射50%CCl4橄榄油混合溶液复制肝纤维化大鼠模型。造模结束后,各组大鼠从第9周开始灌胃相应药物或蒸馏水,每日1次,连续给药4周。实验期间观察大鼠一般情况;计算大鼠肝指数;采用比色法检测大鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、超氧化物歧化酶(SOD)、丙二醛(MDA)的含量;采用HE染色和Masson染色观察大鼠肝组织病理形态学和肝纤维化情况;采用Westernblot法检测肝组织中磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)通路及凋亡相关蛋白表达水平。结果与正常组比较,模型组大鼠饮食量下降,被毛稀疏、蓬乱,反应迟钝,体重增长速率减慢或体重降低;肝指数显著上升(P<0.01);大鼠血清中ALT、AST、MDA含量均显著升高,SOD含量显著降低(P<0.01);HE染色及Masson染色均观察到大鼠肝组织中有大量纤维增生,胶原容积分数显著升高(P<0.01);大鼠肝组织中PI3K、Akt、磷酸化Akt、B细胞淋巴瘤2(Bcl-2)蛋白表达水平均显著下降,Bcl-2相关X蛋白表达水平显著升高(P<0.01)。与模型组比较,安五脂素高、低剂量组及秋水仙碱片组上述指标均显著逆转(P<0.01或P<0.05)。结论安五脂素可能是通过激活PI3K/Akt信号通路降低肝纤维化氧化应激反应、抑制肝细胞凋亡,发挥抗肝纤维化的作用。 |
ABSTRACT: | OBJECTIVE To investigate the effect and mechanism of anwulignan on improving hepatic fibrosis in rats. METHODS Fifty SD rats were randomly divided into the normal group, model group, colchicine tablet group (0.1 mg/kg), and anwulignan high-dose and low-dose groups (2.8 and 0.7 mg/kg), with 10 rats in each group. Except for the normal group, all groups of rats were intraperitoneally injected with 50% CCl4 olive oil mixed solution to replicate the rat model of liver fibrosis. At the end of the modeling, rats in each group were given the corresponding drugs or distilled water intragastrically from the 9th week, once a day, for 4 weeks consecutively. During the experimental period, the general condition of the rats was observed; the liver index was calculated; the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by colorimetric assay; the pathomorphology of the liver tissues and liver fibrosis were observed by HE staining and Masson staining; Western blot was used to detect the expression levels of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway and apoptosis-related proteins in liver tissues. RESULTS Compared with the normal group, the dietary amount of rats in the model group decreased, with sparse and disheveled fur, slow response, and a slower rate of weight growth or weight loss; the liver index was significantly increased (P<0.01); the serum levels of ALT, AST and MDA were significantly increased, and the SOD level was significantly decreased (P<0.01); HE and Masson staining showed that a large amount of fibrous proliferation was present in the liver tissues of the rats, and the collagen volume fraction was significantly increased (P<0.01); the protein expressions of PI3K, Akt, phosphorylated Akt and B-cell lymphoma (Bcl-2) were down-regulated significantly, while the protein expression of Bcl-2-associated X protein was increased significantly (P<0.01). Compared with the model group, the above indexes of the anwulignan high-dose and low-dose groups and the colchicine tablets group were all reversed significantly. CONCLUSIONS Anwulignan may reduce oxidative stress and inhibit hepatocyte apoptosis by activating the PI3K/Akt signaling pathway, and play the role of anti-hepatic fibrosis. |
期刊: | 2023年第34卷第20期 |
作者: | 何秀义;安祯祥;何远利;刘义;何松 |
AUTHORS: | HE Xiuyi,AN Zhenxiang,HE Yuanli,LIU Yi,HE Song |
关键字: | 安五脂素;肝纤维化;磷脂酰肌醇3-激酶/蛋白激酶B通路;氧化应激;凋亡 |
KEYWORDS: | Anwulignan; hepatic fibrosis; PI3K/Akt pathway; |
阅读数: | 43 次 |
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