三七总皂苷后处理减轻兔失血性休克复苏期心肌损伤

Panax notoginseng saponins postconditioning reduces rabbits' hemorrhagic shock and resuscitation myocardial damage

中文关键词: 三七总皂苷  缺血后处理  失血性休克  缝隙连接蛋白  线粒体

英文关键词: Panax notoginseng saponins  Postconditioning  Hemorrhagic shock  Connexin 43  Mitochondria

中文摘要:

      
目的 探讨三七总皂苷（PNS）后处理对兔失血性休克复苏期心肌损伤的影响和机制。

方法 选择雄性新西兰兔30只，11周龄，体质量2.5～3.5 kg。随机分为五组：假手术组（S组）、失血性休克复苏组（H组）、PNS后处理组（P组）、18-β甘草酸（18-AGA）+PNS后处理组（AP组）、18-AGA组（A组），每组6只。S组行气管插管，右侧颈总动脉和右侧股静脉置管，不做放血处理。H组、P组、AP组和A组行气管插管后，制备失血性休克复苏模型。P组于造模成功后45 min给予PNS 100 mg/kg，AP组于造模前腹腔注射18-AGA 75 mg/kg，于造模成功后45 min给予PNS 100 mg/kg，A组造模前腹腔注射18-AGA 75 mg/kg。于复苏1 h时取兔心肌组织，采用Western blot法检测线粒体Cx43含量，采用TUNEL法检测心肌细胞凋亡率，通过透射电镜观察心肌线粒体超微结构，进行线粒体超微结构评分。

结果 与S组比较，H组、AP组、A组心肌线粒体Cx43相对含量明显降低（P＜0.05），H组、P组、AP组、A组心肌细胞凋亡率明显升高，线粒体超微结构评分明显升高（P＜0.05）。与H组比较，P组心肌线粒体Cx43相对含量明显升高，心肌细胞凋亡率明显降低（P＜0.05），AP组、A组心肌线粒体Cx43相对含量明显降低（P＜0.05），P组和AP组粒体超微结构评分明显降低（P＜0.05）。与P组比较，AP组、A组心肌线粒体Cx43相对含量明显降低，心肌细胞凋亡率明显升高，线粒体超微结构评分明显升高（P＜0.05）。S组心肌线粒体膜完整光滑，H组线粒体嵴断裂不清，线粒体完整性丧失，P组线粒体稍肿胀但结构相对完整，AP组线粒体肿胀明显，A组线粒体嵴断裂，线粒体完整性丧失。

结论 三七总皂苷后处理可通过上调线粒体Cx43表达减轻兔失血性休克复苏期心肌损伤。

英文摘要:

      
Objective To investigate the mechanism of panax notoginseng saponins (PNS) postconditioning to reduce apoptosis of cardiomyocytes in hemorrhagic shock and resuscitation.

Methods Thirty male New Zealand rabbits, aged 11 weeks, weighing 2.5-3.5 kg, were randomized into five group: sham operation group(group S), hemorrhagic shock and resuscitation group (group H), PNS postconditioning group (group P), inhibition 18β-glycyrrhetinic acid (18-AGA) + PNS postconditioning group (group AP), 18-AGA group (group A), 6 rabbits in each group. Group S received endotracheal intubation, right common carotid artery and right femoral vein catheterization, without bloodletting treatment. After endotracheal intubation in groups H, P, AP, and A, a hemorrhagic shock resuscitation model were prepared. Group P was given PNS 100 mg/kg 45 minutes after successful modeling. Group AP was intraperitoneally injected 18-AGA 75 mg/kg before modeling, and PNS 100 mg/kg 45 minutes after modeling. Group A was intraperitoneally injected 18-AGA 75 mg/kg before modeling. Myocardial tissues were obtained 1 hours later after the animals were resuscitated. Expression of mitochondrial Cx43 was detected by Western blot, apoptosis of cardiomyocytes was observed by TUNEL. The ultrastructure of myocardial mitochondria was observed under transmission electron microscope and mitochondrial ultrastructure score was performed.

Results Compared with group S, the relative content of mitochondrial Cx43 was significantly decreased in groups H, AP,and A (P < 0.05), the apoptosis rate of cardiomyocytes was significantly increased, mitochondrial ultrastructure scores were significantly increased in groups H, P, AP, and A (P < 0.05). Compared with group H, the relative content of mitochondrial Cx43 was significantly increased, the apoptosis rate of cardiomyocytes was significantly decreased in group P (P < 0.05), the relative content of mitochondrial Cx43 was significantly decreased in groups AP and A (P < 0.05), the granular ultrastructure scores were significantly decreased in groups P and AP (P < 0.05). Compared witn group P, the relative content of mitochondrial Cx43 was significantly decreased, the apoptosis rate of cardiomyocytes was significantly increased, the granular ultrastructure scores were significantly increased in groups AP and A (P < 0.05). Myocardial mitochondria in group S had complete and smooth mitochondrial membrane. Mitochondrial cristae in group H was not clearly broken and mitochondrial integrity was lost. Mitochondria in group P were slightly swollen but relatively complete. The mitochondrial swelling of group AP was obvious. Mitochondrial ridge fracture and mitochondrial integrity loss in group A.

Conclusion PNS postconditioning reduces the myocardial damage in hemorrhagic shock during resuscitation through up-regulating the expression of mitochondrial Cx43.