右美托咪定对大鼠肠缺血再灌注后心肌损伤保护的研究

Dexmedetomidine Protection Myocardial Injury after Intestinal Ischemia-reperfusion in Rats

目的:观察右美托咪定预处理对大鼠肠缺血再灌注诱发的心肌损伤(IIRICI)保护作用及其作用机制。方法:将40只Wistar健康雄性大鼠随机分为:正常对照组(C组),假手术组(S组)、缺血再灌注组(I/R组)、缺血预处理组(P组)和右美托咪定组(D组),每组8只。观察各组左室内压(LVSP)、左心室舒张末期室内压力(LVEDP)、等容收缩期左室内压力上升或等容舒张期下降最大速率(+dp/dtmax,-dp/dtmax)指标;取心脏组织免疫组化观察Caspase-12蛋白,Western-Blot检测p-PERK、p-eIF2α和GRP78蛋白。结果:与C组比较,S组各观察指标均无显著改变,无统计学意义(P>0.05);与C组比较,I/R组、P组、D组中LVSP均明显下降(P<0.05),LVEDP均明显升高(P<0.05);+dp/dtmax、-dp/dtmax均明显减小(P<0.05)。与I/R组比较,P组、D组LVSP均明显升高(P<0.05),LVEDP均明显降低(P<0.05);+dp/dtmax、-dp/dtmax均明显增大(P<0.05)。与C组比较,I/R组、P组、D组中Caspase-12表达均增强,且差异有统计学意义(P<0.05);与I/R组比较,P组、D组中Caspase-12表达均减弱,且差异有统计学意义(P<0.05)。P组与D组相比,各项指标均无显著改变,差异无统计学意义(P>0.05);与C组比较,I/R组、P组、D组中p-PERK、p-eIF2α和GRP78蛋白表达均增强,且差异有统计学意义(P<0.05);与I/R组比较,P组、D组中p-PERK、p-eIF2α和GRP78蛋白表达均减弱,且差异有统计学意义(P<0.05)。结论:心肌缺血预处理与右美托咪定预处理均可明显改善肠缺血再灌注后心肌细胞功能,右美托咪定预处理可能通过抑制心肌内质网应激信号途径PERK/eIF2α/GRP78的激活,进而减轻肠缺血再灌注后心肌细胞凋亡,起到心肌保护作用。

Objective: To investigate the protective effect and mechanism of dexmedetomidine on intestinal ischemia-reperfusion-induced cardiac injury(IIRICI) in rats. Methods: Forty Wistar rats were randomly divided into five groups: normal control group(Group C), sham operation group(Group S), ischemia-reperfusion group(group I/R), ischemic pretreatment group(group P) and right metomidine group(Group D). The left ventricular pressure(LVSP), left ventricular end diastolic pressure(LVEDP), and the maximum rate of increase or decrease of left ventricular pressure(+DP/dtmax,-DP/dtmax) in isovolumic systolic and diastolic period were observed in each group. Caspase-12 protein was detected by immunohistochemistry, p-PERK p-eIF2αand GRP78 protein were detected by Western blot. Results: Compared with group C, each observation index of group S had no significant change, no statistical significance(P>0.05). Compared with group C, LVSP in group I/R, P and D decreased significantly(P<0.05), LVEDP increased significantly(P<0.05);+DP/dtmax and-DP/dtmax decreased significantly(P<0.05). Compared with I/R group, LVSP and LVEDP in group P and D were significantly increased(P<0.05), while +DP/dtmax and-DP/dtmax were significantly increased(P<0.05). Compared with group C, the expression of caspase-12 in group I/R, group P and group D increased, and the difference was statistically significant(P<0.05). There was no significant difference of each observation index between group P and group D(P>0.05);Compared with group I/R, the expression of caspase-12 in group P and group D decreased, and the difference was statistically significant(P<0.05). Compared with group C, the protein expression of p-PERK p-eIF2α and GRP78 in group I/R, group P and group D was increased, and the difference was statistically significant(P<0.05);compared with group I/R, the protein expression of p-PERK p-eIF2α and GRP78 in group P and group D was decreased, and the difference was statistically significant(P<0.05). Conclusion: Myocardial ischemic pretreatment and dexmedetomidine pretreatment can significantly improve myocardial cell function after intestinal ischemia-reperfusion. Dexmedetomidine pretreatment may play a role in myocardial protection by inhibiting the activation of PERK/eIF2α/GRP78, which is the signal pathway of endoplasmic reticulum stress.