性激素对雄性非酒精性脂肪性肝炎小鼠的影响研究

Influence of Sex Hormone on Non-alcoholic Steatohepatitis in Male Mice

目的探讨性激素对蛋氨酸-胆碱缺乏(MCD)饮食诱导非酒精性脂肪性肝炎(NASH)小鼠的影响。方法选用14周龄C57BL/6雄性小鼠50只,采用随机数字表法分为对照组、MCD组、睾丸切除组、睾丸切除+雄激素组、睾丸切除+雌激素组5组,每组10只。对照组和MCD组小鼠行假手术,睾丸切除组、睾丸切除+雄激素组、睾丸切除+雌激素组小鼠行睾丸切除术,恢复2 d后,对照组小鼠饲喂MCD对照饮食,其余4组小鼠饲喂MCD饮食,建立MCD饮食诱导C57BL/6雄性NASH小鼠模型;性别干预:睾丸切除+雄激素组小鼠皮下注射丙酸睾酮,睾丸切除+雌激素组小鼠皮下注射苯甲酸雌二醇。比较各组小鼠非酒精性脂肪性肝病活动度评分(NAS)及血清睾酮、雌二醇、ALT、AST水平。结果 MCD组、睾丸切除组、睾丸切除+雄激素组、睾丸切除+雌激素组NAS总分秩均值均大于对照组(P<0.05),睾丸切除组、睾丸切除+雌激素组NAS总分秩均值均小于MCD组(P<0.05),睾丸切除+雌激素组NAS总分秩均值均小于睾丸切除组、睾丸切除+雄激素组(P<0.05)。睾丸切除组和睾丸切除+雌激素组小鼠血清睾酮水平均低于对照组、MCD组、睾丸切除+雄激素组(P<0.05),睾丸切除+雌激素组小鼠血清雌二醇水平均高于对照组、MCD组、睾丸切除组、睾丸切除+雄激素组(P<0.05);MCD组、睾丸切除组、睾丸切除+雄激素组、睾丸切除+雌激素组小鼠血清ALT、AST水平均高于对照组(P<0.05),睾丸切除组小鼠血清ALT、AST水平均低于MCD组(P<0.05),睾丸切除+雌激素组小鼠血清ALT、AST水平均低于MCD组、睾丸切除组、睾丸切除+雄激素组(P<0.05)。结论在MCD饮食诱导C57BL/6雄性NASH小鼠模型中,雌激素可减轻NASH病情严重程度,而雄激素的作用还有待商榷。

Objective To study the influence of sex hormone on non - alcoholic steatohepatitis （NASH） induced by methionine and choline -deficient （MCD） diet. Methods 50 C57BL/6 male mice of 14 weeks were selected and randomly di- vided into control group, MCD group, orchideetomy group, orchideetomy ＋ male hormone group and orehideetomy ＋ female hor- mone group, with each group 10 mice. The control group and MCD group were given sham operation, while the other three groups were given orehideetomy. Two days after the operation, the control group was given MCD control diet, while the other four groups were given MCD diet to establish C57BL/6 NASH model. The orehideetomy ＋ male hormone group was given subcutaneous injec- tion of testosterone propionate, while the orchideetomy ＋ female hormone group was given subcutaneous injection of estradiol ben- zoate. The NAS, serum testosterone, estradiol, ALT and AST levels were compared between the groups. Results The NAS of the control group was lower than the other four groups （ P 〈 0. 05 ）, and the NAS in orchidectomy group and orchidectomy ＋ female hormone group was lower than the MCD group （ P 〈 0. 05 ）, and the NAS in orchidectomy ＋ female hormone group was lower than the orchidectomy group and orchidectomy ＋ male hormone group （ P 〈 0. 05 ） . The testosterone level in orchidectomy group and orchidectomy ＋ female hormone group was lower than the control group, MCD group and orchidectomy ＋ male hormone group （ P 〈 0. 05 ）, and the estradiol level in orchidectomy ＋ female hormone group was higher than the other four groups （ P 〈 0. 05 ） . The ALT and AST levels of the control group were lower than the other four groups （P 〈 0. 05 ） . The ALT and AST levels of the orchidectomy group were lower than the MCD group （ P 〈 0. 05 ）, and the ALT and AST levels of the orchidectomy ＋ female hormone group were lower than the MCD group, orchidectomy group and orchidectomy ＋ male hormone group （ P 〈 0. 05 ）. Conclusion The female hormone can alleviate NASH induced by MCD diet in C57BL/6 male mice, while the effect of male hor- mone remains to be studied.