小檗碱对大鼠肝硬化肝组织IFN-γ表达与端粒酶活性的影响

Effects of Berberine on the Expression of IFN-γ and Activity of Telomerase in Rat Liver Cirrhosis Tissue

目的探讨小檗碱抑制血吸虫肝硬化组织恶性变潜能的作用及其机制。方法将80只大鼠感染日本血吸虫尾蚴,随机分为A、B、C、D组,每组20只。模型对照组(A组)不作任何治疗;吡喹酮组(B组)感染尾蚴6周后给予吡喹酮500 mg·kg-1·d-1灌胃2 d;小檗碱组(C组)感染尾蚴6周后给予小檗碱150 mg·kg-1·d-1灌胃6周;小檗碱+吡喹酮组(D组)在感染尾蚴6周后给予吡喹酮500 mg·kg-1·d-1灌胃2 d,再以小檗碱150 mg·kg-1·d-1灌胃6周。另取10只大鼠作为正常对照组(E组)。第12周末分别留取各组大鼠肝组织,检测肝脏Ⅰ、Ⅲ型胶原及干扰素-γ(IFN-γ)含量、端粒酶活性与端粒酶反转录酶(TERT)表达情况。结果与A组比较,B组和C组肝纤维化程度均减轻,肝组织IFN-γ含量显著升高,端粒酶活性与TERT表达水平降低(P<0.05)。与B组比较,C组大鼠肝纤维化程度、IFN-γ含量及端粒酶活性、TERT表达水平无明显差异(P>0.05)。与B组、C组比较,D组大鼠肝纤维化程度进一步减轻,肝组织IFN-γ含量显著升高(P<0.05),端粒酶活性及TERT表达水平显著降低(P<0.05)。结论小檗碱可通过调节大鼠肝组织内免疫应答,促进IFN-γ表达,抑制肝组织TERT表达及端粒酶活性,可配合吡喹酮对大鼠晚期血吸虫肝硬化起协同、增效作用。

Objective To study the inhibitory effect and mechanism of berberine on the malignant potential of liver cir-rhosis tissue due to schistosoma. Methods Eighty rats infected with schistosoma japonicum were equally divided into A, B, C and D groups, twenty rats in each. Group A was taken as model control without any treatment. Group B was treated with praziqu-antel at 500 mg·kg^-1 ·d^-1 for 2 days. Group C was treated with berberine at 150 mg·kg^-1 ·d^-1 for 6 weeks. Group D was trea-ted with berberine at 150 mg·kg^-1 ·d^-1 for 6 weeks followed by praziquantel treatment at 500 mg·kg^-1 ·^d-1 for 2 days. Ten rats were taken as normal control group （group E）. At 12th week, all rats were sacrificed and parts of liver tissues were pre-served. The contents of IFN-γ,typeⅠ collagen, type Ⅲ collagen, telomerase reverse transcriptase （TERT ）and the activity of te-lomerase in liver tissue before and after treatments were detected. Results Compared to the group A, the therapy of praziqu-antel or berberine singly reduced the contents of typeⅠand type Ⅲ collagens,TERT and the activity of telomerase and greatly raised the content of IFN-γ（P〈0. 05 ）. Compared to the group B, there was no difference on the contents of IFN-γ,typeⅠ colla-gen,type Ⅲ collagen,TERT and the activity of telomerase in liver tissue between two groups（P〉0. 05）. Compared to the group C or group B, the contents of typeⅠ collagen,type Ⅲ collagen,TERT and the activity of telomerase in liver tissue were obviously reduced and the content of IFN-γ was conspicuously elevated （P〈0. 05 ） in the group D. Conclusion Berberine can inhibit the malignancy by inhibiting the expression of TERT and the activity of telomerase via regulating immune response and promoting the expression of IFN- γ in liver tissue. Berberine may be used in symergism with the insecticidal treatment for advanced schisto-somal hepatic cirrhosis.