细胞周期素依赖性蛋白激酶抑制剂治疗实验性单纯疱疹性脑炎的效果及其机制

Effect and its mechanism of cyclin dependent protein kinase inhibitor treatment on experimental herpes simplex encephalitis

目的探讨细胞周期素依赖性蛋白激酶(CDK)抑制剂(Olomoucine)治疗实验性单纯疱疹性脑炎(HSE)效果及其机制。方法45只小鼠随机分为1型单纯疱疹病毒(HSV-1)假感染组、感染对照组和Olo-moucine治疗组,每组15只。应用流式细胞术测定各组脑细胞表面抗原CD11b的表达;使用逆转录-聚合酶链反应方法检测肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)的表达;TUNEL染色检测神经细胞凋亡,脑组织病理切片观察组织形态学变化。另40只小鼠HSV-1感染后随机分为Acyclovir治疗组和Olomoucine治疗组,每组20只;2周后应用Kaplan-Meier法进行生存率比较。结果HSV-1感染后脑组织中CD11b阳性细胞、TNF-α、IL-6表达较假感染组显著增高(均P<0.01);TUNEL阳性细胞数明显增多;脑组织细胞变性、出血及炎性细胞浸润。Olomoucine治疗后,脑组织中CD11b阳性细胞、TNF-α、IL-6表达明显降低(均P<0.01),神经细胞凋亡减少,脑组织病理改变减轻。Olomoucine治疗组生存率较Acydovir治疗组显著提高(P<0.05)。结论Olo-moucine治疗可以减弱HSE小鼠脑组织的免疫病理损伤,保护神经细胞,改善其预后。

Objective To investigate the effect and its mechanism of cyclin dependent protein kinase inhibitor Olomoucine treatment on experimental herpes simplex encephalitis （ HSE ）. Methods 45 mice, were randomly assigned to HSV-1 sham-infected group （ n = 15 ）, HSV-1 infected control group （ n = 15 ） and Olomoucine treated group （n = 15 ）. Flow cytometry was used to detect the expression of brain cells surface antigen CD1 lb. The reverse transcription polymerase chain reaction （RT-PCR） to detect the expression of tumor necrosis factor-ix （TNF-ct）and Interleukin-6 （IL-6）. TUNEL method was adopted to detect neural cells apoptosis. Pathologic slices of brain tissues were used to identify tissue morphology differences. The survival rates were compared between the treatment groups Acyclovir （n = 20） and Olomoueine （n = 20） by the method of Kaplan-Meier 2 weeks after HSV-1 infection. Results After HSV-1 infection, the expression of brain tissue CD11b, TNF-α, IL-6 were significantly increased compared with sham-infected group （all P〈 0.01 ）. The TUNEL-positive cells were obviously increased. The cells degenerated, hemorrhaged and inflanmmatory cell infiltrated were observed in brain tissue. After Olomoucine treatment, the expression of brain tissue CD11 b, TNF-α, IL-6 were significantly reduced （ all P 〈0.01） , and less neuronal apoptosis. The attenuated brain tissue pathological changes were observed. The survival rate was higher in Olomoucine treated group than in Acyclovir treated group （P 〈0.05 ）. Conclusion Olomoucine treatment can weaken the immunopathological damage and protect neurone, then improve the prognosis of HSE mice.