凋亡抑制剂zVAD对脑梗死小鼠外周血白细胞端粒长度的影响

目的探讨凋亡抑制剂z VAD对脑梗死小鼠外周血白细胞端粒长度的影响。方法将80只雄性C57BL/6小鼠,随机分为10组:即Model组(3组共24只)、z VAD组(3组共24只)、Sham组(3组共24只)和Control组(8只)。Model组与z VAD组均采用线栓法构建小鼠大脑中动脉栓塞模型,1 h后完成再灌注。再灌注后z VAD组立即腹腔注射浓度为2.3mmol/L的z VAD 10ml/kg进行干预。Sham组则暴露颈动脉后缝合皮肤进行假手术操作。Control组不进行任何操作。造模后,分别于不同时间点对各组小鼠进行改良神经功能损伤程度评分(m NSS),评分后立即取血,提取外周血基因组DNA,real-time PCR法检测相对端粒长度。Control组则选取再灌注后72 h时间点,进行同期同质的评分与测量。结果术后48 h和72 h,z VAD组的m NSS评分均明显低于相应的Model组,但仍高于相应的Sham组(P0.05)。术后72 h,z VAD组相对端粒长度明显长于Model组(P0.05),且基本与Sham组和Control组的长度持平(P0.05)。结论凋亡抑制剂z VAD可减缓脑梗死小鼠外周血白细胞端粒长度缩短,并对神经功能损伤起到一定的保护作用。

Influence of Apoptosis Inhibitor-zVAD on Telomere Length of Peripheral Leukocytes in Mice with Cerebral Ischemia

Objective To explore the influence of the apoptosis inhibitor-zVAD on the telomere length of peripheral leukocytes in mice with cerebral ischemia.Methods Eighty male C57BL/6 mice were randomly divided into Model group (24 mice divided into 3 group equally),zVAD group (24 mice divided into 3 group equally),Sham group (24 mice divided into 3 group equally) and Control group (8mice).Modelgroup and zVAD group were conducted by the intraluminal filament technics and reperfusion was made 1 h later.zVAD group was given 2.3 mmol/L zVAD with 10 ml/kg by peritoneal injection.Sham group was conducted with only sham operation,no operation was carried out in Control group.At different time points after operation (24 h,48 h,72 h),neurological function was evaluated according to modified Neurological Severity Score (mNSS),genomic DNA was extracted from blood.Telomere length was measured by real-time PCR.Results The mNSS of the model group and zVAD group was significantly higher than that of the sham group at 24 h,48 h and 72 h(P＜0.05).The mNSS of administration groups was significantly lower than that of the model group at 48h and 72h (P＜0.05).At 72 h after operation,the telomere length of the model group mice was shortened when compared with the zVAD group,sham group and control group,and the difference was statistically significant (all P＜0.05),but there was no significant difference between the zVAD group,sham group and control group (P＞0.05).Conclusion The apoptosis inhibitor-zVADcan help protect the telomere length of peripheral leukocytes in mice with cerebral ischemia.