Fas基因介导的细胞凋亡在帕金森病发病中的作用

Role of Fas gene-mediated apoptosis in pathogenesis of Parkinson′s disease

目的探讨Fas基因介导的细胞凋亡在帕金森病发病中的作用。方法(1)将45只大鼠随机分为空白对照组、帕金森病组、Fas小干扰RNA(siRNA)组,每组15只。空白对照组大鼠于左侧脑黑质内注入生理盐水3μL,帕金森病组大鼠于左侧脑黑质内注入3μL的5μg/μL 6-羟多巴胺(6-OHDA),Fas siRNA组大鼠于左侧脑黑质内注入Fas siRNA 3μL(1.0 nmol/L),2天后同侧注射同计量的6-OHDA。采用免疫组化检测3组大鼠中脑阳性多巴胺细胞数,并采用PCR法检测3组大鼠中脑组织Fas mRNA表达情况。(2)将153例帕金森病患者根据Hoehn-Yahr分期分为轻度组21例、中度组85例、重度组47例,再选取177例健康者作为对照组,比较4组血清可溶性Fas(sFas)及其配体(sFasL)水平。结果(1)Fas siRNA组大鼠旋转率较帕金森病组减少,空白对照组、Fas siRNA组、帕金森病组酪氨酸羟化酶(TH)阳性细胞计数依次降低,Fas mRNA表达水平依次升高(均P<0.05)。帕金森病组与Fas siRNA组大鼠的Fas-mRNA表达水平与TH阳性细胞呈负相关性(均P<0.05)。(2)中度组和重度组患者血清sFas和sFasL水平均高于对照组和轻度组,且重度组以上指标均高于中度组;帕金森患者sFas和sFasL水平与Hoehn-Yahr分期呈正相关(均P<0.05)。结论Fas表达上调可促进细胞凋亡,从而参与帕金森病的发生和发展。

Objective To investigate the role of Fas gene-mediated apoptosis in the pathogenesis of Parkinson′s disease.Methods(1)Forty-five rats were randomly divided into blank control group,Parkinson′s disease group and Fas small interfering RNA(siRNA)group,with 15 rats in each group.Rats in the blank control group were injected with 3μL of normal saline into the left substantia nigra,rats in the Parkinson′s disease were injected with 3μL of 5μg/μL 6-hydroxydopamine(6-OHDA)into the left substantia nigra,rats in the Fas siRNA group were injected with 3μL of 1.0 nmol/L Fas siRNA into the left substantia nigra and received ipsilateral injection of 3μL of 5μg/μL 6-OHDA two days later.The number of brain dopamine-positive cells was determined by immunohistochemistry in the three groups,and the expression of brain tissue Fas mRNA was detected by PCR in the three groups.(2)Totally 153 patients with Parkinson′s disease were divided into mild(n=21),moderate(n=85)and severe(n=47)groups according to the Hoehn-Yahr stages,and 177 healthy subjects were selected as control group.The levels of serum soluble Fas(sFas)and its ligand sFasL were compared among the four groups.Results(1)The Fas siRNA group yielded a decreased rotation rate than the Parkinson′s disease group.The number of tyrosine hydroxylase(TH)-positive cells decreased and the expression level of Fas mRNA increased in the sequence of the blank control group,the Fas siRNA group and the Parkinson′s disease group(all P<0.05).The expression level of Fas mRNA negatively correlated with TH-positive cells in the Parkinson′s disease and Fas siRNA groups(all P<0.05).(2)The moderate and severe groups exhibited higher serum sFas and sFasL levels than the control and mild groups,and the severe group reported higher aforementioned indices than the moderate group;in patients with Parkinson′s disease the levels of sFas and sFasL positively correlated with Hoehn-Yahr stages(all P<0.05).Conclusion Upregulation of Fas expression can promote apoptosis,thus involved in the occurrence and development of Parkinson′s disease.