目的 探讨排钱草总生物碱通过抑制核因子-κB(NF-κB)信号通路对急性肝衰竭(ALF)大鼠的保护作用及其机制。方法 Wistar雄性大鼠随机分成对照组、模型组和排钱草总生物碱组, ip D-半乳糖胺(D-GalN)(400 mg/kg) /脂多糖(LPS)(10μg/kg)建立ALF大鼠模型。对照组和模型组大鼠均ig 3 g/kg生理盐水;排钱草总生物碱组大鼠ig排钱草总生物碱3g/kg,给予药物干预14 d后,观察排钱草总生物碱对大鼠一般情况的影响,测定ALF大鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平并用HE染色观察排钱草总生物碱对ALF大鼠肝组织病理学的影响,采用Western blotting法检测各组大鼠肝组织NF-κB及Iκβ磷酸化的表达水平。结果 排钱草总生物碱可有效降低模型大鼠血清ALT、AST水平(P<0.001); HE染色显示,排钱草总生物碱可以使模型大鼠肝组织坏死程度减轻,可见部分增生肝细胞,炎性浸润减轻。Western blotting结果显示,排钱草总生物碱可以抑制模型大鼠肝组织p-NF-κB和p-Iκβ表达升高,从而抑制NF-κB通路的激活。结论 排钱草总生物碱可能通过抑制NF-κB通路发挥其对ALF大鼠的保肝作用。

Objective To explore the protective effect of total alkaloid of Phyllodium pulchellum on rats with acute liver failure by inhibiting NF-κB signaling pathway, and to further reveal the protective mechanism.Methods Wistar male rats were divided into control group, model group, and total alkaloid of P. pulchellum group. ALF model was made by ip D-GalN (400 mg/kg)/LPS (10 μg/kg). Rats in control group and model group were ig normal saline 3 g/kg, and rats in total alkaloid of P. pulchellum group were ig total alkaloid of P. pulchellum 3 g/kg. After 14 d of drug intervention, the effects of total alkaloid of P. pulchellum on general condition of rats were observed. ALT and AST levels in serum of rats with ALF were determined, and HE staining was used to observe the effects of total alkaloid of P. pulchellum on liver histopathology of rats with ALF. The phosphorylation levels of NF-κB and Ikβ in liver tissues were detected by Western blotting.Results Total alkaloid of P. pulchellum can decrease ALT and AST in serum (P < 0.001). HE staining showed that total alkaloid of P. pulchellum can reduce the necrosis of rat liver tissue, and some hyperplasia liver cells can be seen, and inflammatory infiltration can be reduced. Western blotting showed that total alkaloid of P. pulchellum can inhibit the increase of p-NF-κB and p-Ikβ, and thus inhibit the activation of NF-κB pathway.Conclusion Total alkaloid of P. pulchellum may exert its hepatoprotective effect by inhibiting NF-κB pathway.

R285.5

国家自然科学基金青年项目(81803884);广东省中医药局科研项目(20191215)