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覃妮,周柳,李俊伟,吴腾,李秋萍,陶晓静,黄灵聪,韦西玲,张洪平,陆世银.脱氢卡维丁对CCl4诱导的肝纤维化大鼠的改善作用[J].湖南中医药大学学报英文版,2024,44(2):220-226.[Click to copy
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| 脱氢卡维丁对CCl4诱导的肝纤维化大鼠的改善作用 |
| 覃妮,周柳,李俊伟,吴腾,李秋萍,陶晓静,黄灵聪,韦西玲,张洪平,陆世银 |
| (柳州市中医医院(柳州市壮医医院), 中药(壮瑶药)制剂研发重点实验室, 广西 柳州 545026;柳州市中医医院(柳州市壮医医院), 中药(壮瑶药)制剂开发工程技术研究中心, 广西 柳州 545026) |
| 摘要: |
| 目的 探讨脱氢卡维丁对四氯化碳（carbon tetrachloride， CCl4）诱导的肝纤维化大鼠的改善作用及可能机制。方法 将SD大鼠随机分为正常组、模型组、水飞蓟宾组（30 mg/kg）、脱氢卡维丁组（50 mg/kg），每组6只。除正常组外，其他各组采用30%CCl4橄榄油溶液（1 m L/kg）腹腔注射复制肝纤维化模型，每周2次，连续14周。各给药组于造模第13、14周每天按设定剂量灌胃相应药物进行干预。正常组与模型组大鼠灌胃等体积的生理盐水。末次给药12 h后，测定各组大鼠肝脾指数；采用HE染色与Masson染色观察肝组织病理学变化，比色法检测大鼠血清丙氨酸转氨酶（alanine aminotransferase， ALT）、天冬氨酸转氨酶（aspartate aminotransferase， AST）、丙二醛（malondialdehyde， MDA）、超氧化物歧化酶（superoxide dismutase， SOD）的含量；采用ELISA检测血清透明质酸（hyaluronic acid， HA）、层黏连蛋白（laminin， LN）、Ⅲ型前胶原蛋白（typeⅢprocollagen， PCⅢ）及Ⅳ型胶原蛋白（collagenⅣ， ColⅣ）的表达水平；Western blot法检测肝组织转化生长因子-β1（transforming growth factor-β1， TGF-β1）、α-平滑肌肌动蛋白（α-smooth muscle actin， α-SMA）、E-钙黏蛋白（E-cadherin）、N-钙黏蛋白（N-cadherin）的表达情况。结果 与正常组相比，模型组大鼠肝脾指数显著增加（P<0.001），肝组织纤维化进展明显，胶原容积分数明显增加（P<0.001），血清中ALT、AST、MDA、LN、HA、PCⅢ和ColⅣ水平显著升高（P<0.001），SOD明显下降（P<0.001）；肝组织TGF-β1、α-SMA及N-cadherin蛋白表达水平明显上升（P<0.001），Ecadherin蛋白表达明显下降（P<0.001）。与模型组比较，脱氢卡维丁组大鼠肝脾指数明显降低（P<0.001），肝组织病理学损伤和纤维增生有效改善，胶原容积分数明显下降（P<0.001），血清ALT、AST、MDA含量显著降低（P<0.001），血清SOD的表达水平明显升高（P<0.001），LN、HA、PCⅢ、ColⅣ的表达明显下调（P<0.05，P<0.001），肝组织TGF-β1、α-SMA和N-cadherin蛋白表达显著下降（P<0.001），而E-cadherin蛋白表达明显升高（P<0.001）。结论 脱氢卡维丁对肝纤维化大鼠具有良好的改善作用，其机制可能与调节氧化应激反应、下调N-cadherin、α-SMA、TGF-β1蛋白表达及上调E-cadherin蛋白表达有关。 |
| 关键词: 脱氢卡维丁 肝纤维化 氧化应激 E-钙黏蛋白、N-钙黏蛋白 α-平滑肌肌动蛋白 转化生长因子-β1 |
| DOI：10.3969/j.issn.1674-070X.2024.02.007 |
| Received:July 12, 2023 |
| 基金项目:广西中医药大学自然科学基金面上项目（2020MS055）；柳州市科技攻关与新产品试制（2020NBAA0802）。 |
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| Alleviating effects of dehydrocavidine on carbon tetrachloride-induced hepatic fibrosis in rats |
| TAN Ni,ZHOU Liu,LI Junwei,WU Teng,LI Qiuping,TAO Xiaojing,HUANG Lingcong,WEI Xiling,ZHANG Hongping,LU Shiyin |
| (Liuzhou Key Laboratory for Preparation Development of Chinese Medicines (Zhuang and Yao Medicines), Liuzhou Chinese Medical Hospital (Liuzhou Hospital of Zhuang Medicine), Liuzhou, Guangxi 545026, China;Liuzhou Engineering Technology Research Center for Preparation Development of Chinese Medicines (Zhuang and Yao Medicines), Liuzhou Chinese Medical Hospital (Liuzhou Hospital of Zhuang Medicine), Liuzhou, Guangxi 545026, China) |
| Abstract: |
| Objective To investigate the alleviating effects and their possible mechanism of dehydrocavidine on carbon tetrachloride(CCl4)-induced hepatic fibrosis in rats.Methods SD rats were randomized into normal group, model group, silibinin group(30 mg/kg), and dehydrocavidine group(50 mg/kg), with six rats in each group. Except for normal group, the other three groups were injected intraperitoneally with 30% CCl4olive oil solution(1 mL/kg) to establish the hepatic fibrosis model, twice a week for14 weeks. At the 13th and 14th weeks of modeling, each medication group was given the corresponding drug at the set dose intragastrically every day. Meanwhile, normal and model groups were given the equal volume of normal saline intragastrically. After12 h of the last administration, the rat hepatic and splenic tissue were collected to measure the hepatic and splenic indexes; HE staining and Masson staining were used to observe the histopathological changes of the liver; colorimetric method was carried out to determine the content of alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), and superoxide dismutase(SOD) in rat serum. ELISA was performed to measure the expression levels of serum hyaluronic acid(HA), laminin(LN),type Ⅲ procollagen(PCⅢ) and collagen Ⅳ(Col Ⅳ); Western blot was applied to examining the protein expression levels of transforming growth factor β1(TGF-β1), α-smooth muscle actin(α-SMA), E-cadherin, and N-cadherin in the liver tissue.Results Compared with normal group, the hepatic and splenic indexes of rats in model group significantly increased(P<0.001), the degree of hepatic fibrosis was remarkable, and the collagen volume fraction was significantly elevated(P<0.001); meanwhile, the serum levels of ALT, AST,MDA, LN, HA, PCⅢ, and Col Ⅳ were fairly higher(P<0.001), while the level of SOD was obviously lower(P<0.001); the protein expression levels of TGF-β1, α-SMA, and N-cadherin in the liver tissue were significantly up-regulated(P<0.001), while that of Ecadherin was obviously down-regulated(P<0.001). Compared with model group, the hepatic and splenic indexes of rats in dehydrocavidine group were significantly reduced(P<0.001), the histopathological damage and fibrous hyperplasia were effectively alleviated, and the collagen volume fraction decreased significantly(P<0.001); the serum levels of ALT, AST, and MDA were significantly lower(P<0.001),while that of SOD was significantly higher(P<0.001); the serum expression levels of LN, HA, PCⅢ, and Col Ⅳ were obviously upregulated(P<0.05, P<0.001); the protein expression levels of TGF-β1, α-SMA, and N-cadherin in the liver tissue markedly decreased(P<0.001), while that of E-cadherin significantly increased(P<0.001).Conclusion Dehydrocavidine can alleviate hepatic fibrosis in rats significantly, the mechanism of which may be related to the intervention in the oxidative stress, down-regulation of N-cadherin,α-SMA, and TGF-β1 protein expressions, and up-regulation of E-cadherin protein expression in the liver tissue. |
| Key words: dehydrocavidine hepatic fibrosis oxidative stress E-cadherin N-cadherin α-smooth muscle actin transforming growth factor β1 |
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