丹参酮ⅡA磺酸钠对小鼠感染人巨细胞病毒肝炎的干预研究

Study on the Effect of Tanshinone Ⅱ A Sodium Sulfonate in Mice Infected with Human Cytomegalovirus Hepatitis

目的:观察丹参酮ⅡA磺酸钠对小鼠感染人巨细胞病毒肝炎的干预作用。方法:选择健康小鼠根据随机原则分为正常对照组、模型对照组以及丹参酮ⅡA磺酸钠组,每组各72只。其中,模型对照组及丹参酮ⅡA磺酸钠组接种后各组大鼠进行配对饲养,观察受精时间并等待各组新生小鼠出生。新生小鼠出生后10日进行治疗,每对小鼠选择生产的新生小鼠1只,共12只;丹参酮ⅡA磺酸钠组予以腹腔注射丹参酮ⅡA磺酸钠1.0mL/10g/d,共治疗28日;模型对照组及正常对照组均给予等体积细胞维持液DMEM,使用方法、剂量及使用频率和丹参酮ⅡA磺酸钠组完全相同至实验结束。比较各组小鼠病理学结果、血清肝纤维化指标、肝功能五项以及P450亚型酶活性。结果:与正常对照组相比,模型对照组及丹参酮ⅡA磺酸钠组血清Ⅳ型胶原、层粘连蛋白、透明质酸以及Ⅲ型前胶原水平较高(P<0.05),血清天冬转氨酶、胆汁酸、总胆红素、谷氨酰转移酶、丙氨酸转氨酶水平较高(P<0.05),P450亚型酶中CYP2E1、CYPIA2、CYP2D6、CYP2C9、CYP3A4活性较高(P<0.05);与模型对照组相比,丹参酮ⅡA磺酸钠组血清Ⅳ型胶原、层粘连蛋白、透明质酸以及Ⅲ型前胶原水平较低(P<0.05),血清天冬转氨酶、胆汁酸、总胆红素、谷氨酰转移酶、丙氨酸转氨酶水平较低(P <0.05),CYP2E1、CYPIA2、CYP2D6、CYP2C9、CYP3A4较低(P<0.05)。结论:丹参酮ⅡA磺酸钠能够下调P450亚型酶活性,降低药物代谢时对肝脏的毒性作用,促进肝功能修复,对感染人巨细胞病毒肝炎小鼠有明确的治疗作用,有望为感染人巨细胞病毒肝炎的临床治疗提供新的干预方法。

Objective：To investigate the effect of Tanshinone Ⅱ A sodium sulfonate in mice infected with human cytomegalovirus hepatitis.Methods：The healthy mice were randomly divided into normal control group,model control group and tanshinone Ⅱ A sodium sulfonate group,72 rats in each group.Rats in control group and tanshinone Ⅱ A sodium sulfonate group were inoculated to observe the time of fertilization and wait for the birth of newborn mice.Newborn mice were treated 10 days after birth,and each mouse was selected to produce a total of 1 newborn mice（n=12）.Tanshinone A sodium sulfonate group was injected with tanshinone A sodium sulfonate 1.0 mL/10 g/d for 28 days;The control group and normal control group were given the same volume of cell maintenance fluid DMEM,the method of use,dosage and frequency of use and tanshinone Ⅱ A sodium sulfonate group is exactly the same as the end of the experiment.The pathological results,serum liver fibrosis indexes,liver function of five groups and the activity of P450 isoforms were compared.Results：Compared with the normal control group,the levels of type IV collagen,laminin,hyaluronic acid and type ⅡI procollagen（P〈0.05）were higher in the model control group and tanshinone Ⅱ A sodium sulfonate group,the serum aspartate aminotransferase,bile acid,total bilirubin,alanine aminotransferase and alanine aminotransferase levels were higher（P〈0.05）,The activity of CYP2 E1,CYPIA2,CYP2 D6,CYP2 C9 and CYP3 A4 in the P450 isoforms were higher（P〈0.05）;Compared with the model group,the levels of serum type IV collagen,laminin,hyaluronic acid and type ⅡI procollagen（P〈0.05）were lower in tanshinone A sodium sulfonate group,the serum aspartate aminotransferase,bile acid,total bilirubin,alanine aminotransferase,alanine aminotransferase levels were lower（P〈0.05）,the CYP2 E1,CYPIA2,CYP2 D6,CYP2 C9 and CYP3 A4 levels were lower（P〈0.05）.Conclusion：Tanshinone Ⅱ A sodium sulfonate can downregulate P450 subtype enzymes,toxic effects on the liver to reduce drug metabolism,promote liver function recovery,has a definite therapeutic effect on infection of human cytomegalovirus hepatitis in mice,is expected to provide a new method for the intervention of human cytomegalovirus hepatitis in clinical treatment.