Nrf2/HO-1通路介导的及己根与雷公藤水提取物致大鼠心脏毒性的比较研究

Nrf2/HO-1 Pathway-mediated Cardiotoxicity in Rats Induced by Water Extracts of Chloranthus Serratus Root and Tripterygium

目的:比较及己根与雷公藤水提取物致大鼠心脏毒性大小并探讨其毒性机制.方法:将30只SD雄性大鼠随机均分成空白(KB)组、及己根水提取物(GS)组、雷公藤水提取物(LS)组.GS组、LS组大鼠分别用及己根水提取物或雷公藤水提取物溶液灌胃,KB组大鼠给予等量蒸馏水,每天1次,连续灌胃14天.绘制体重变化曲线;计算心脏脏器指数;测定血清中CK、CK-MB、LDH、AST、α-HBDH含量及心脏匀浆中T-SOD和MDA含量;HE染色法观察各组大鼠心脏组织病理变化;免疫组化法检测心脏组织中ICAM-1阳性表达情况;蛋白免疫印迹法检测心脏组织中HO-1、Nrf2蛋白表达情况.结果:与KB组相比,GS组、LS组大鼠体重增长较KB组缓慢,且LS组大鼠实验后期体重出现负增长;GS组、LS组大鼠心脏脏器指数均升高,但仅LS组的升高具有显著性.与KB组和GS组相比,LS组CK、CK-MB、LDH、AST、α-HBDH、MDA、ICAM-1均明显升高,T-SOD及HO-1、Nrf2蛋白表达均极显著性降低.组织病理学结果显示,GS组存在少量炎性细胞浸润,而LS组观察到明显的血管扩张充血,心肌纤维排列紊乱,纤维间出血及部分细胞核固缩现象.结论:雷公藤水提取物引起的大鼠心脏毒性较大,其毒性机制可能与氧化应激及Nrf2/HO-1通路的抑制有关;及己根作为抗炎药有进一步的研究价值.

Objective:To compare the cardiotoxicity induced by water extracts of Chloranthus serratus(C.serratus)root and tripterygium in rats and explore the toxicity mechanisms.Methods:Thirty male SD rats were randomly divided into the blank(KB)group,the C.serratus root extract(GS)group and the tripterygi?um water extract(LS)group.The rats in the GS and LS groups were orally administered with the GS or LS suspension,respectively.And the rats in the KB group were received the same amount of distilled water,once a day for 14 consecutive days.The curves of weight change were drawn,the cardiac indexes were calcu?lated,and the contents of CK,CK-MB,LDH,AST and α-HBDH in serum and the contents of T-SOD and MDA in homogenate were measured.Hematoxylin Eosin(H&E)staining method was used to observe the pathological changes of heart tissues in each group of the rats.ICAM-1 positive expression in cardiac tissues was detected by immunohistochemistry.Western blot was used to detect the expression of HO-1 and Nrf2 proteins.Results:Compared with the KB group,the weight gain of the GS and LS groups was slower than that of the KB group,and the body weight of the LS group showed a negative increase at the later stage of the experiment.The cardiac indexes of the rats in the GS and LS groups increased,but only the LS group was significant.Compared with the KB and GS groups,the contents of CK,CK-MB,LDH,AST,α-HBDH,MDA,and ICAM-1 were significantly increased in the LS group,and the T-SOD content and HO-1 and Nrf2 protein expression were extremely reduced.Histopathological results showed that there was a small amount of inflammatory cell infiltration in the GS group,while obvious vasodilation and congestion,disordered myocardial fiber arrangement,interfiber hemorrhage and partial cell nuclear contraction were observed in the LS group.Conclusion:The LS have stronger cardiotoxicity to rats than the GS,and its toxic mechanisms may be related to oxidative stress and the suppression of Nrf2/HO-1 pathway,and the C.serratus root has further research value as an anti-inflammatory drug.