阿托伐他汀对实验性自身免疫性脑脊髓炎大鼠脑组织TIM-3、TIM-1表达的影响

The Effect of Atorvastatin on TIM-3,TIM-1 in Rats Brain with Experimental Autoimmune Encephalomyelitis

目的:观察阿托伐他汀对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)Wistar大鼠的发病情况、组织病理变化及脑组织内T细胞免疫球蛋白和黏液域蛋白-3(TIM-3)、T细胞免疫球蛋白和黏液域蛋白-1(TIM-1)表达水平的影响。方法:将30只雌性Wistar大鼠随机分为佐剂组、EAE组、阿托伐他汀组,以豚鼠脊髓匀浆(GPSCH)诱发制备大鼠EAE模型,并于给予GPSCH当日开始1次/d灌服0.1%PBS溶液1.5ml/只(佐剂组和EAE组)和含阿托伐他汀的0.1%PBS溶液,1次/d,剂量为8mg/(kg·d),连续13d,观察EAE症状并评分,用逆转录-聚合酶链反应(RT-PCR)法检测Tim-1mRNA、Tim-3mRNA在脑组织中的表达。结果:阿托伐他汀组发病率降低、临床症状减轻,体重下降减少(P<0.05);与佐剂组比较,EAE组TIM-3mRNA明显上升(P<0.05),阿托伐他汀组TIM-3mRNA较EAE组明显下降(P<0.05);与佐剂组比较,EAE组TIM-1mRNA下降(P<0.05),阿托伐他汀组TIM-1mRNA较EAE组上升(P<0.05)。结论:EAE大鼠TIM-3上升,TIM-1下降,提示其在EAE发病机制中发挥作用,通过下调TIM-3、上调TIM-1的表达,可能是阿托伐他汀对EAE保护作用机制之一。

Objective：To observe atorvastatin on experimental autoimmune encephalomyelitis（Experimental Autoimmune Encephalomyelitis,EAE）,the incidence of Wistar rats,histopathological changes and brain tissue T cell immunoglobulin and mucus domain protein-3（the TIM-3） T-cell immune globulin and mucus-domain protein-1（TIM-1） expression levels.Method：30 female Wistar rats were randomly divided into three groups：the adjuvant group,EAE group,and atorvastatin statin group.The preparation of guinea pig spinal cord homogenate（GPSCH） induced rat EAE model,and give GPSCH at the beginning of the day once daily gavage 0.1% PBS solution 1.5 ml（adjuvant group and EAE group） containing atorvastatin 0.1% PBS solution,once a day.Dose of 8 mg/（kgod）,for 13 consecutive days to observe the EAE symptoms and rate,using reverse transcription-polymerase chain reaction（RT-PCR） assay the expression of Tim-1 mRNA in Tim-3 mRNA in the brain tissue.Result：Atorvastatin atorvastatin group decreased incidence,clinical symptoms,reduced weight loss（P0.05）.The comparison with adjuvant group,EAE group the TIM-3 mRNA increased（P0.05）,atorvastatin the statin group the TIM-3 mRNA compared EAE group decreased（P0.05）.The comparison with adjuvant group,EAE group the TIM-1 mRNA decreased（P0.05）,atorvastatin the statin group the TIM-1 mRNA increased compared with the EAE group,and a statistically significant（P0.05）.Conclusion：TIM-3 increased and TIM-1 decreased in EAE rats,which suggests that atorvastatin plays a role in EAE pathogenesis.This may be a protection mechanism of atorvastatin for EAE.