枯草溶菌素转换酶9对缺血再灌注心肌内质网应激的影响及机制研究

目的 研究枯草溶菌素转换酶9(PCSK9)对缺血再灌注大鼠心肌内质网应激的影响及可能的作用机制，为临床研究提供新的研究方向。 方法 选取健康SD雄性30只，建立心肌缺血再灌注模型，按照随机数字表法分为假手术组、模型组和PCSK9组，各10只。建模成功24 h后，PCSK9组大鼠给予30 μg PCSK9皮下注射，假手术组、模型组大鼠给予等体积的生理盐水进行皮下注射。检查各组大鼠用药干预结束后1 d LVEDP、心肌梗死面积率、LDH、CK-MB、CK、细胞凋亡率、增殖、GRP78、CHOP、cleaved-caspase3水平。 结果 PCSK9组干预后LVEDP(8.83±0.28) mm Hg (1 mm Hg=0.133 kPa)]、心肌梗死面积率(15.21±4.75)%]低于模型组干预后(13.65±0.38) mm Hg、(37.35±8.16)%]，高于假手术组干预后(7.72±0.43) mm Hg、0%，F=731.290，t=7.420，均P＜0.001]；PCSK9组干预后LVSP(127.94±7.67) mm Hg]高于模型组干预后(79.84±6.44) mm Hg]，低于假手术组干预后(145.53±9.08) mm Hg，F=189.830,P＜0.001]。模型组、PCSK9组干预后细胞凋亡率、LDH、CK-MB、CK水平以及GRP78、CHOP、cleaved-caspase3蛋白表达高于假手术组，细胞增殖率低于假手术组(均P＜0.05)。 结论 PCSK9对缺血再灌注大鼠心肌内质网应激有抑制作用，通过调控GRP78、CHOP、cleaved-caspase3蛋白，改善大鼠心功能和心肌梗死状况。 

Effect and mechanism of PCSK9 on endoplasmic reticulum stress in ischemia-reperfusion myocardium

Objective To study the effect of Bacillus subtilis lysis converting enzyme 9 (PCSK9) on myocardial endoplasmic reticulum stress and its possible mechanism, and to provide a new research direction for clinical research. Methods Thirty healthy male SD rats were selected to establish myocardial ischemia-reperfusion model. According to the method of random number table, rats were divided into three groups:sham operation group, model group and PCSK9 group. Twenty-four hours after the successful modeling, the PCSK9 group rats were injected subcutaneously with 30 μg PCSK9, while the sham operated group rats and the model group rats were injected subcutaneously with normal saline of equal volume. LVEDP, myocardial infarct area rate, LDH, CK-MB, CK, apoptosis rate, proliferation, GRP78, CHOP, and cleaved caspase 3 levels were examined at the end of the intervention. Results The LVEDP(8.83±0.28) mm Hg] and myocardial infarction area rate(15.21±4.75)%] in the PCSK9 group were lower than those in the model group(13.65±0.38) mm Hg, (37.35±8.16)%] and higher than those in the sham operation group(7.72±0.43) mm Hg, 0%], F=731.290, t=7.420, all P<0.001. In the PCSK9 group, LVSP(127.94±7.67) mm Hg] was higher than that in the model group(79.84±6.44) mm Hg], lower than that in the sham operation group. The prognosis of the sham operation group was (145.53±9.08) mm Hg (F=189.830, P<0.001). The apoptosis rate, LDH, CK-MB, CK level, GRP78, CHOP and cleaved caspase-3 protein expression in the model group and the PCSK9 group were higher than those in the sham operation group, and the cell proliferation rate was lower than that in the sham operation group (all P<0.05). Conclusion PCSK9 can regulate GRP78, CHOP and caspase-3 protein, inhibit the stress of myocardial endoplasmic reticulum and improve the cardiac function and myocardial infarction.