阿托伐他汀在致死型约氏疟原虫感染的肝脏病理损伤中的作用研究

Role of atorvastatin in liver pathological damage of lethal Plasmodium yoelii infection

目的:探讨阿托伐他汀(AVA)在治疗致死型约氏疟原虫(P. y 17XL)感染的肝脏病理损伤中的作用。方法:以P. y 17XL感染BALB/c小鼠为研究对象,口服AVA单药或联合青蒿琥酯(AS),动态观察原虫血症和生存率。HE和组化染色观察肝脏病理改变。流式细胞术检测肝淋巴细胞数量和CXCR6、NKG2D表达水平。结果:P. y 17XL感染后第7天,对照组感染率迅速上升至61. 8%,AVA组感染率为41. 2%,明显低于对照组(P<0. 05)。AVA组原虫血症峰值延迟出现,联合AS用药可延长小鼠生存时间。HE结果显示,P. y 17XL感染导致疟色素在肝脏大量沉积,肝细胞出现嗜酸性坏死。与对照组相比,AVA组疟色素在肝组织沉积明显减少。流式结果显示,CD3^+、CD4^+和CD8^+T细胞数量明显增加(P <0. 05)。CXCR6在CD4^+、CD8^+和NKT细胞表达明显上调(P<0. 05,P<0. 01,P<0. 05)。NKG2D在CD8+T细胞和NKT细胞中表达水平明显升高(P<0. 05)。结论:AVA在改善疟疾肝脏病理损伤中发挥重要作用。

Objective:To investigate the role of Atorvastatin(AVA) treatment on liver pathological damage caused by lethal Plasmodium yoelii 17XL( P.y 17XL). Methods: The treatment of AVA or combined with Artesunate (AS) were orally taken in BALB/c mice infected with P.y 17XL.The parasitemia and survival rate were dynamically observed.Hepatic pathological changes were observed using HE and immunohistochemistry staining methods.The numbers of hepatic lymphocytes and the expression levels of CXCR6 and NKG2D in lymphocytes were analyzed by flow cytometry. Results: In control group,the parasitemia rapidly increased to 61.8% on the seventh day after P.y 17XL infection.However,the parasitemia was 41.2% in AVA group,which was significantly lower than that in control group ( P <0.05).The peak of parasitemia was delayed in AVA group compared with that in control group,and the survival time was prolong in mice treatment with AVA combination of AS.HE results showed that P.y 17XL infection resulted in the deposition of malaria pigments in the liver and eosinophilic necrosis of hepatocytes.Compared with the control group,the deposition of malaria pigments was significantly reduced in liver tissue of AVA group.In AVA group,the number of CD3^+,CD4^+ and CD8^+T cells increased significantly ( P <0.05).The expression of CXCR6 was significantly increased on CD4^+,CD8^+ and NKT cells ( P <0.05, P <0.01, P <0.05).The expression level of NKG2D was significantly enhanced on CD8^+T cells and NKT cells ( P <0.05). Conclusion: AVA treatment plays an important role on improving liver pathological damage caused by plasmodium infection.