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[摘要]
目的:基于PI3K/Akt/mTOR 信号通路探讨蓝盆花的抗大鼠肝纤维化作用及机制。方法:将SD大鼠随机分为对照组,模型组和蓝盆花高、中、低剂量组,通过腹腔注射CCl4橄榄油溶液诱导肝纤维化。造模4周后,分别按照高、中、低剂量灌胃给予蓝盆花溶液。生化鉴定检测大鼠ALT、AST活性;通过HE染色观察大鼠肝脏组织病理学变化;通过western blot检测肝纤维化标志物E-cadherin、α-SMA和Collagen Ⅰ,同时检测PI3K、Akt以及mTOR蛋白表达。结果:干预4周后,蓝盆花高、中剂量组的肝细胞变性、坏死和肝小叶结构破坏等肝损伤表现明显减轻,大鼠血清ALT、AST水平明显下降。肝纤维化可显著增加α-SMA和Collagen Ⅰ的表达,并降低E-cadherin的表达。与模型组相比,高、中剂量组大鼠肝纤维化标志物α-SMA和Collagen Ⅰ蛋白水平显著降低,E-cadherin蛋白水平显著升高,p-PI3K、p-Akt、p-mTOR蛋白水平显著降低。结论:蒙药蓝盆花对肝纤维化具有一定的治疗效果,可能通过抑制PI3K/Akt/mTOR信号通路,发挥其对肝脏的保护作用。
[Key word]
[Abstract]
OBJECTIVE: To investigate the anti-fibrotic effect and mechanism of Scabiosa comosa on rat liver fibrosis based on PI3K/Akt/mTOR signaling pathway. METHODS: SD rats were randomly divided into control group, model group and high, medium and low dose groups. Liver fibrosis was induced by intraperitoneal injection of CCl4 olive oil solution. After 4 weeks of modeling, Scabiosa comosa solution was given by intragastric administration at high, medium and low doses respectively. The activities of ALT and AST were detected by biochemical identification. The histopathological changes of liver were observed by HE staining. The markers of liver fibrosis E-cadherin, α-SMA and Collagen I were detected by westernblot, while the protein expressions of PI3K, Akt and mTOR were detected. RESULTS: After 4 weeks of intervention, hepatocyte degeneration, necrosis and destruction of hepatic lobular structure in high and medium dose groups of Scabiosa comosa were significantly alleviated, and serum ALT and AST levels were significantly decreased. Liver fibrosis significantly increased the expression of α-SMA and Collagen I, and decreased the expression of E-cadherin. Compared with model group, the protein levels of α-SMA and Collagen I markers of liver fibrosis in high and medium dose groups were significantly decreased, the protein levels of E-cadherin were significantly increased, the protein levels of p-PI3K, p-Akt and p-mTOR were significantly decreased. CONCLUSION: Mongolian medicine Scabiosa comosa has a certain therapeutic effect on liver fibrosis, which may exert its protective effect on liver by inhibiting PI3K/Akt/mTOR signaling pathway.
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[基金项目]
内蒙古自然科学基金重大项目(No.2023ZD15);国家自然科学基金(No.82160794、82160703);内蒙古自然科学基金(No.2020 MS08046、2020MS08106 );内蒙古自治区 "草原英才 "工程;中国科学院西部之光青年学者计划;内蒙古自治区自然科学基金重大项目(No.2021ZD14);内蒙古自治区科技计划项目(No.2020GG0138);内蒙古自治区 "草原英才 "领军人才工程。