水蛭对肝内胆汁淤积大鼠模型法尼醇X受体通路的调节作用

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Abstract Objective To study the regulatory effect of leech on farnesol X receptor (FXR) pathway in rat model of intrahepatic cholestasis. Methods Forty SPF male SD rats aged eight weeks were selected and divided into normal group, model group, ursodeoxycholic acid (UDCA) group, leech high-dose group and leech low-dose group according to random number table method, with eight rats in each group. The UDCA group was intragastrically administered with UDCA solution at a dose of 60 mg/kg, and the leech high-dose and low-dose groups were intragastrically administered with Leech Granules at a dose of 50 mg/kg and 20 mg/kg, once a day, for consecutive seven days，the normal group and the model group were given the same amount of normal saline. Except normal group, rats in other groups were given 100 mg/kg α-isothiocyanate (ANIT) on the fifth day of intragastric administration for model formation. Gastric administration for three days, once a day, the normal group was given the same amount of normal saline. Blood samples were collected from the abdominal aorta 24 h after the last administration, and serum levels of alanine aminotransferase (ALT), ascorbic aminotransferase (AST), total bilirubin (TBil) and total bile acid (TBA) were detected. Hepatic tissue was collected for microscopic examination by HE staining to observe the pathological conditions of the liver. The mRNA and protein expressions of FXR and its downstream small heterodimer chaperone receptor (SHP), uridine diphosphate glucuronide transfer 2B4 (UGT2B4) and bile salt output pump (BSEP) were detected by real-time fluorescence quantitative PCR and Western blot. Results The levels of ALT, AST and TBil in serum of leech high-dose group were lower than those in model group, with statistically significant differences (all P ＜ 0.05). There was no statistical significance in TBA level between leech high-dose group and model group (P ＞ 0.05). The levels of serum AST, TBA and TBil in leech low-dose group were lower than those in model group, with statistically significant differences (all P ＜ 0.05). There was no significant difference in ALT level between leech low-dose group and model group (P ＞ 0.05). The serum AST level of UDCA group was lower than that of model group, and the difference was statistically significant (all P ＜ 0.05). There were no statistically significant differences in ALT, TBA and TBil levels between UDCA group and model group (P ＞ 0.05). Compared with model group, liver tissue damage of rats in leech high-dose and low-dose groups was alleviated. The mRNA expressions of FXR, BSEP, UGT2B4 and SHP in leech high-dose and low-dose groups and UDCA group were higher than those in model group, with statistically significant differences (all P ＜ 0.05). The protein expressions of FXR, BSEP, UGT2B4 and SHP in leech high-dose and low-dose groups were higher than those in model group, and the differences were statistically significant (all P ＜ 0.05). There was no statistically significant difference in protein levels between UDCA group and model group (P ＞ 0.05). Conclusion Leech can relieve intrahepatic cholestasis induced by ANIT and alleviate liver tissue damage. Leech can protect liver cells by upregulating FXR gene expression, promoting the upregulation of SHP, UGT2B4 and BSEP gene expression and inhibiting cholestasis pathway, thus providing effective drugs for clinical treatment of intrahepatic cholestasis.

Key words： Leech Farnesoil X receptor Intrahepatic cholestasis α-isothiocyanate

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	LIU Yuqing1 CAI Xin1 QIN Renwu2 WANG Yao3 LUO Lei4 YANG Fan5

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LIU Yuqing1 CAI Xin1 QIN Renwu2 WANG Yao3 LUO Lei4 YANG Fan5. Regulation effect of leech on farnesol X receptor pathway in rat model of intrahepatic cholestasis[J]. 中国医药导报, 2021, 18(5): 4-9.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2021/V18/I5/4

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