目的 探討排錢草總生物堿通過抑制核因子-κB(NF-κB)信號通路對急性肝衰竭(ALF)大鼠的保護(hù)作用及其機(jī)制。方法 Wistar雄性大鼠隨機(jī)分成對照組、模型組和排錢草總生物堿組, ip D-半乳糖胺(D-GalN)(400 mg/kg) /脂多糖(LPS)(10μg/kg)建立ALF大鼠模型。對照組和模型組大鼠均ig 3 g/kg生理鹽水;排錢草總生物堿組大鼠ig排錢草總生物堿3g/kg,給予藥物干預(yù)14 d后,觀察排錢草總生物堿對大鼠一般情況的影響,測定ALF大鼠血清中丙氨酸氨基轉(zhuǎn)移酶(ALT)、天門冬氨酸氨基轉(zhuǎn)移酶(AST)水平并用HE染色觀察排錢草總生物堿對ALF大鼠肝組織病理學(xué)的影響,采用Western blotting法檢測各組大鼠肝組織NF-κB及Iκβ磷酸化的表達(dá)水平。結(jié)果 排錢草總生物堿可有效降低模型大鼠血清ALT、AST水平(P<0.001); HE染色顯示,排錢草總生物堿可以使模型大鼠肝組織壞死程度減輕,可見部分增生肝細(xì)胞,炎性浸潤減輕。Western blotting結(jié)果顯示,排錢草總生物堿可以抑制模型大鼠肝組織p-NF-κB和p-Iκβ表達(dá)升高,從而抑制NF-κB通路的激活。結(jié)論 排錢草總生物堿可能通過抑制NF-κB通路發(fā)揮其對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

國家自然科學(xué)基金青年項目(81803884);廣東省中醫(yī)藥局科研項目(20191215)