CD8~+ T细胞在早期内毒素血症对心功能的损害作用

目的:探讨CD8+T细胞在早期内毒素血症心脏损伤中的浸润及其对心功能的影响。方法:野生雄性小鼠20只随机分为野生对照组和野生内毒素血症组,每组各10只;CD8敲除雄性小鼠10只,随机分为CD8敲除对照组和CD8敲除内毒素血症组,每组各5只。对照组均给予0.9%氯化钠液腹腔注射,内毒素血症组均给予脂多糖腹腔注射。6 h显微超声检测射血分数及短轴缩短分数;即刻处死并收取野生对照组及野生内毒素血症组各3只小鼠心脏组织,流式细胞技术检测心脏细胞悬液中巨噬细胞(F4/80+细胞)及CD8+T细胞、CD4+T细胞分布;其余小鼠心脏组织进行病理切片HE染色,观察心肌纤维断裂及炎症细胞浸润。结果:与野生对照组相比,野生内毒素血症组射血分数及短轴缩短分数显著降低(均为P<0.05);野生内毒素血症组F4/80+细胞、CD4+T细胞及CD8+T细胞均显著增加(均为P<0.05)。与野生内毒素血症组相比,CD8基因敲除内毒素血症组射血分数及短轴缩短分数均显著升高(均为P<0.05)。结论:急性内毒素血症导致心肌纤维损伤、心功能不全,心脏组织CD8+T等炎症细胞浸润;而缺乏CD8+T细胞时则减轻内毒素血症导致的心功能损伤,提示CD8+T细胞在急性内毒素血症诱导的心功能不全早期发挥重要作用。

The effect of CD8+ T cells on endotoxemia-induced cardiac disfunction

Objective:To evaluate the involvement and effect of CD8+T cells in endotoxemia induced cardiac injury.Methods:Two groups of C57BL/6 wild-type mice were injected with saline(n=10) and LPS(n=10) separately;two groups of CD8 knockout mice were injected with saline and LPS separately.Cardiac function was evaluated by ultrasound 6 hr after LPS injection.Flow cytometry analysis was used to determine F4/80+,CD8+T cells,CD4+T cells infiltration in the heart of wild-type LPS injected or control group(n=3 for each group).The rest mice were sacrificed and hearts were undergone H&E staining analysis.Results:The ultrasound result showed that the LPS injection significantly deceased cardiac function(as evaluated by ejection fraction(EF%) and FS%,P<0.05),but CD8 knockout prevented LPS-induced cardiac dysfunction.H&E staining showed LPS injection induced inflammatory cells infiltration and FACS analysis demonstrated that LPS injection stimulated F4/80+,CD4+T cells and CD8+T cells infiltration into the heart(P<0.05).Conclusion:Endotoxemia caused cardiac dysfunction by inducing the infiltration of inflammatory cells especially CD8+T cells into the heart,however,knockout of CD8 prevented endotoxemia-induced heart dysfunction.Our results indicated that CD8+T cells may play an important role in endotoxemia-induced heart failure,however the underlie mechanism need to be further investigated.