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白屈菜碱对四氯化碳诱导肝纤维化模型大鼠的改善作用及机制
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| 篇名： | 白屈菜碱对四氯化碳诱导肝纤维化模型大鼠的改善作用及机制 |
| TITLE： | Improvement Effects of Chelidonine on CCl 4-induced Hepatic Fibrosis Model Rats and Its Mechanism |
| 摘要： | 目的：研究白屈菜碱对四氯化碳诱导肝纤维化模型大鼠的改善作用及可能机制。方法：将48只大鼠按随机数字表法随机分成正常对照组，模型组，白屈菜碱低、中、高剂量组（0.125、0.25、0.50mg/kg）和阳性对照组（护肝片，0.42g/kg），每组8只。除正常对照组外，其余各组大鼠均采用腹腔注射四氯化碳-橄榄油溶液8周建立肝纤维化模型。于造模第5周开始，正常对照组和模型组大鼠灌胃水，各给药组大鼠灌胃相应药液，每天1次，连续10周。末次灌胃后，计算大鼠肝指数；测定大鼠血清中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、透明质酸（HA）和肝组织中羟脯氨酸（Hyp）水平；观察大鼠肝组织中胶原纤维蛋白染色情况；测定大鼠肝组织中α-平滑肌肌动蛋白（α-SMA）、微管相关蛋白1轻链3（LC3）、p62蛋白表达水平和磷脂酰肌醇3激酶（PI3K）、蛋白激酶B（Akt）、哺乳动物雷帕霉素靶蛋白（mTOR）的磷酸化水平，以及上述蛋白对应的mRNA表达水平。结果：与正常对照组比较，模型组大鼠肝指数，血清中AST、ALT、HA、Hyp水平，肝组织中胶原纤维蛋白阳性染色面积百分比和α-SMA、LC3-Ⅱ的mRNA及其蛋白表达水平均显著升高（P＜0.05）；p62蛋白表达水平，PI3K、Akt、mTOR的蛋白磷酸化水平以及p62、PI3K、Akt、mTORmRNA表达水平均显著降低（P＜0.05）。与模型组比较，白屈菜碱低剂量组大鼠PI3K、mTOR的蛋白磷酸化水平均显著降低（P＜0.05）；白屈菜碱中、高剂量组上述指标（除中剂量组肝指数、HA水平外）的变化均被显著逆转（P＜0.05）。结论：白屈菜碱对四氯化碳所致大鼠肝纤维化具有一定的改善作用；其机制可能与激活PI3K/Akt/mTOR信号通路、抑制细胞自噬有关。 |
| ABSTRACT： | OBJECTIVE：To study the improvement eff ects and p otential mechanism of chelidonine on CCl 4-induced hepatic fibrosis model rats. METHODS ：According to the random number table method ，a total of 48 rats were randomly divided into normal control group ，model group ，chelidonine low-dose ，middle-dose and high-dose groups （0.125，0.25，0.50 mg/kg），positive control group （Liver-protecting tablet ，0.42 g/kg），with 8 rats in each group. Except for normal control group ，other groups were given CCl 4-olive oil solution intraperitoneally for 8 weeks to induce hepatic fibrosis model. From the fifth week of modeling ， normal control group and model group were given water intragastrically ；administration groups were given relevant medicine intragastrically，once a day ，for consecutive 10 weeks. After last intragastric administration ，hepatic index of rats was calculated. The levels of aspartate aminotransferase （AST），alanine aminotransferase （ALT）and hyaluronic acid （HA）in serum and the level of hydroxyproline （Hyp）in liver tissue were determined. The staining of collagen fibrin in rat liver was observed. The protein expression of α-smooth muscle actin （α-SMA），microtubule-associated protein 1 light chain 3（LC3）and p 62 as well as the phosphorylation level of phosphoinositide 3 kinase（PI3K），protein kinase B （Akt）and mammalian target of rapamycin （mTOR）in liver tissue were determined ；mRNA expression corresponding to above protein were also determined. RESULTS ：Compared with normal control group ，the hepatic index ，the serum levels of AST ，ALT，HA and Hyp ，the percentage of positive staining area for collagen fibrin ，the mRNA and protein expression of α-SMA and LC 3- Ⅱ were increased significantly （P＜0.05）. Protein expression of p 62，phosphorylation levels of PI 3K，Akt and mTOR as well as mRNA expression of p 62，PI3K，Akt and mTOR were significantly down-regulated （P＜0.05）. Compared with model group ，phosphorylation levels of PI 3K and mTOR were decreased significantly in chelidonine low-dose group （P＜0.05）. The changes of above indexes in chelidonine middle-dose and high-dose groups （except for liver index ， HA level in middle-dose group ） were reversed significantly （P＜0.05）. CONCLUSIONS：Chelidonine can attenuate CCl 4-induced liver fibrosis in rats ；the mechanism of it may be associated with activating PI 3K/Akt/mTOR signaling pathway and inhibiting autophagy. |
| 期刊： | 2021年第32卷第23期 |
| 作者： | 李晓明，王文豹，郭丽娜，宋波，董巍，徐天娇，王晓丽 |
| AUTHORS： | LI Xiaoming ，WANG Wenbao ，GUO Lina，SONG Bo，DONG Wei，XU Tianjiao ，WANG Xiaoli |
| 关键字： | 白屈菜碱；肝纤维化；磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路；自噬 |
| KEYWORDS： | Chelidonine；Hepatic fibrosis ；PI3K/Akt/mTOR signaling path way；Autophagy |
| 阅读数： | 124 次 |
| 本月下载数： | 5 次 |
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