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何首乌水提取物对大鼠连续28天经口给药后的肝毒性研究:胆汁淤积相关机制

[Study on hepatotoxicity of aqueous extracts of Polygonum multiflorum in rats after 28-day oral administration: cholestasis-related mechanism].

作者信息

Wang Tao, Wang Jia-ying, Zhou Zhi-xing, Jiang Zhen-zhou, Li Yan-yan, Zhang Liang, Zhang Lu-yong

出版信息

Zhongguo Zhong Yao Za Zhi. 2015 Jun;40(11):2163-7.

PMID:26552174
Abstract

OBJECTIVE

To study the effect of aqueous extracts of Polygonum multiflorum (AEPM) on bile acid synthesis, metabolism and transfer-related molecules in rat liver and the hepatotoxicity-related mechanism of P. multiflorum.

METHOD

Sprague-Dawley rats were orally administered with 30, 60 g x kg(-1) APEM once everyday for consecutively 28 days. At the end of the experiment, mRNA and protein expressions of hepatic MRP3, MRP2, BSEP, FXR and CYP7A1 were detected by Real-time PCR and Western blot

RESULT

Compared with the normal group, the AEPM high dose group showed significant increases in mRNA expressions of hepatic MRP3 and BSEP of male rats (P < 0.05); AEPM high and low dose groups revealed a notable decrease in mRNA expressions of hepatic FXR (P < 0.05) and remarkable rises in mRNA expressions of hepatic MRP3, MRP2, BSEP, CYP7A1 among female rats (P < 0.05). According to the test results of western blot assay, AEPM high and low dose groups showed consistent changes in protein and mRNA expressions hepatic MRP3, MRP2, BSEP, FXR, CYP7A1.

CONCLUSION

The 28 oral administration with AEPM in rats showed a certain effect on expressions of bile acid synthesis, metabolism and transfer-related proteins, as well as cholestatic or choleretic effects in the mRNA expression.

摘要

目的

研究何首乌水提取物(AEPM)对大鼠肝脏胆汁酸合成、代谢及转运相关分子的影响以及何首乌的肝毒性相关机制。

方法

将Sprague-Dawley大鼠每天口服给予30、60 g·kg⁻¹的AEPM,连续28天。实验结束时,通过实时荧光定量PCR和蛋白质免疫印迹法检测肝脏MRP3、MRP2、BSEP、FXR和CYP7A1的mRNA和蛋白质表达。

结果

与正常组相比,AEPM高剂量组雄性大鼠肝脏MRP3和BSEP的mRNA表达显著升高(P<0.05);AEPM高、低剂量组雌性大鼠肝脏FXR的mRNA表达显著降低(P<0.05),肝脏MRP3、MRP2、BSEP、CYP7A1的mRNA表达显著升高(P<0.05)。根据蛋白质免疫印迹法检测结果,AEPM高、低剂量组肝脏MRP3、MRP2、BSEP、FXR、CYP7A1的蛋白质和mRNA表达变化一致。

结论

大鼠连续28天口服AEPM对胆汁酸合成、代谢及转运相关蛋白的表达有一定影响,在mRNA表达上有胆汁淤积或利胆作用。

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