右美托咪定对肺缺血/再灌注损伤小鼠内质网应激相关分子Caspase-12表达的影响

目的：探讨右美托咪定（DEX）对肺缺血/再灌注（I/R）损伤小鼠内质网应激（ERS）相关分子天冬氨酸特异性半胱氨酸蛋白酶-12（Caspase-12）表达的影响。方法：选用C57BL/6J小鼠复制在体左肺原位I/R损伤模型。随机将40只小鼠分为4组（n=10）：假手术组（sham组），I/R损伤组（I/R组），生理盐水对照组（NS组），右美托咪定干预缺血/再灌注组（DEX组）。DEX组在夹闭小鼠左肺门30 min前经腹腔注射DEX 25 μg/kg，NS组为用同DEX组等体积的生理盐水替代DEX，其余操作同DEX组。3 h肺再灌注结束后，留取左肺。测定肺组织湿/干重比（W/D）及总肺含水量（TLW），光镜观察肺组织形态学改变，对肺组织进行损伤评估（IQA）。原位末端标记（TUNEL）法检测组织细胞凋亡指数（AI），蛋白免疫印迹法（Western blot）和逆转录-聚合酶链反应（RT-PCR）分别检测Caspase-12、葡萄糖调节蛋白78（grp78）蛋白和mRNA表达水平。结果：与sham组比，I/R组和NS组肺W/D、TLW、IQA、AI均明显升高（P<0.01），肺组织形态结构破坏明显，Caspase-12、grp78蛋白和mRNA表达量增加（P<0.01）；I/R组与NS组相比，两组Caspase-12、grp78蛋白和mRNA表达量无明显差异（P>0.05）。DEX组与I/R组比，W/D、TLW、IQA和AI均有下降（P<0.01或P<0.05），肺组织形态学改变明显减轻，Caspase-12和grp78蛋白和mRNA表达量下降（P<0.01）。结论：DEX可有效缓解小鼠肺缺血/再灌注性损伤，其机制可能与其对抗ERS中Caspase-12引起的细胞凋亡有关。

Effect of dexmedetomidine on expression of endoplasmic reticulum stress-related Caspase-12 in lung ischemia/reperfusion injury mice

Objective: To investigate the effect of dexmedetomidine (DEX) on expression of endoplasmic reticulum stress (ERS)-related cysteinyl aspirate specific proteinase-12 (Caspase-12) in lung ischemia/reperfusion (I/R) injury mice. Methods: Forty C57BL/6J mice were randomly divided into 4 groups:sham operation group (sham group),ischemia/reperfusion injury group (I/R group), normal salinecontrol group (NS group), ischemia/reperfusion + dexmedetomidine group (DEX group). Dexmedetomidine was infused intraperitoneally into the mice to stablish situ left pulmonary I/R injury mouse model. In NS group, the isometric dexmedetomidine was replaced by normal saline,other operations were as the same as the DEX group. After reperfusion 3 hours, the lung tissue wet/dry weight (W/D), the total lung water content (TLW) of the left lung tissues were determined. The lung tissue morphology changes were observed by light microscopy and the damage assessment(IQA) was taken. The structure changes and the apoptosis index (AI) of the lung tissues were evaluated by TUNEL method. The protein and mRNA expression of Caspase-12 and grp78 in lung tissues were detected by Western blot and reverse translate-PCR. Results: Compared with the sham group, the W/D, TLW, IQA, AI, lung tissue structure damages, and the expression of Caspase-12 and grp78 protein and mRNA obviously raised both in I/R group and NS group (P<0.01 or P<0.05). Compared with I/R group, the W/D, TLW, IQA, AI of DEX group were all decreased, the demaged lung tissue morphology changes were significantly reduced, the protein and mRNA expression level of Caspase-12 and grp78 in DEX group were decreased (P<0.01). Conclusion: DEX can effectively relieve the lung I/R injuries in mice, which maybe associated with inhibition of pneumocyte apoptosis induced by ERS-related Caspase-12 pathway.