抑制LSD1酶活性对HBV模型小鼠的作用

Effects of inhibiting the lysine specific demethylase 1 enzyme activity in hepatitis B virus model mouse

目的研究组蛋白赖氨酸去甲基化酶1(LSD1)酶活性下降对乙型肝炎病毒(HBV)模型小鼠的作用。方法尾静脉高压注射重组HBV1.3质粒建立HBV小鼠模型;将雌性BALB/c小鼠随机分为正常组、模型组、LSD1小干扰RNA(siRNA)处理组和反苯环丙胺(TCP)治疗组。取各组小鼠外周血,通过酶联免疫吸附试验、全自动微粒子化学发光法和Real-Time PCR检测小鼠体内乙肝表面抗原(hepatitis B surface antigen,HBsAg)和HBV DNA的表达;免疫组织化学法检测HBsAg在肝脏中的分布;Western blotting检测小鼠脾淋巴细胞LSD1的表达。结果 HBV模型小鼠造模成功;LSD1 siRNA处理组和TCP治疗组小鼠HBsAg、HBV DNA和LSD1的表达水平均较模型组明显下降(P<0.01),肝组织中HBsAg的分布也明显减少。结论抑制LSD1酶活性对HBV模型小鼠体内HBV的清除有一定的作用。

Objective To study the effects of inhibiting the lysine specific demethylase 1 （LSD1） enzyme activity in hepatitis B virus （HBV） model mouse. Methods The BALB/C mice were injected recombinant plasmid HBV1.3 via tail vein to establish HBV mouse model. The female BALB/C mice were randomly divided into normal control group, model group, LSD1 small interfering RNA （siRNA） treatment group, and tranylcypromine （TCP） treatment group. The expressions of hepatitis B surface antigen （HBsAg） and HBV DNA in the peripheral blood of all mice were quantitatively detected by enzyme-linked immuno sorbent assay, chemical luminescent method, and RT-PCR. The distribution of HBsAg in liver was detected by immunohistochemistry. The expression of LSD1 in splenic lymphocytes was detected by Western blotting. Results HBV mouse model was successfully established. Compared to model group, expressions of HBsAg, HBV DNA, and LSD1 were significantly lower in LSD1 siRNA treatment group and TCP treatment group （P 〈 0.01）. And the distribution of HBsAg in liver also decreased remarkably. Conclusion Inhibiting the LSD1 enzyme activity plays a key role in elimination of HBV in HBV model mouse.