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| PI3K/Akt信号通路在富氢水减轻心肺转流致大鼠心肌损伤中的作用 |
| Role of PI3K/Akt signaling pathway in hydrogen-rich solution induced reduction of myocardial injury caused by cardiopulmonary bypass in rats |
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| DOI：10.12089/jca.2022.05.014 |
| 中文关键词: 心肌损伤 心肺转流 富氢水 PI3K/Akt信号通路 |
| 英文关键词: Myocardial injury Cardiopulmonary bypass Hydrogen-rich solution PI3K/Akt signaling pathway |
| 基金项目:辽宁省重点研发计划项目（2020JH2/10300051） |
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| 摘要点击次数: 966 |
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| 中文摘要: |
目的 评价磷脂酰肌醇3激酶/蛋白激酶B（PI3K/Akt）信号通路在富氢水（HRS）减轻心肺转流（CPB）致大鼠心肌损伤中的作用。
方法 清洁级成年雄性SD大鼠40只，10～12周龄，体重350～400 g。采用随机数字表法分为四组：假手术组（S组）、CPB组（C组）、HRS处理组（H组）和PI3K抑制剂组（P组），每组10只。S组仅进行血管穿刺置管，置管后通过尾静脉注射生理盐水6 ml/kg，机械通气90 min，其余各组建立无血预充心脏不停跳CPB模型，CPB 60 min。CPB前60 min，P组通过腹腔内注射PI3K抑制剂6 ml/kg（LY294002，5 μg/ml）。CPB前30 min，C组通过尾静脉注射生理盐水6 ml/kg，H组和P组通过尾静脉注射HRS 6 ml/kg。四组均于CPB停机2 h后取相应标本进行检测。采用Masson染色法观察心肌组织形态学变化；测定大鼠心肌含水量；采用ELISA法测定血浆心肌损伤标记物 [心肌肌钙蛋白I（cTnI）、乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）]和炎性因子[白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）]以及心肌组织氧化应激指标[丙二醛（MDA）、髓过氧化物酶（MPO）、氧化物歧化酶（SOD）]浓度；采用Western blot法检测心肌组织凋亡相关蛋白[B细胞淋巴瘤-2蛋白（Bcl-2）、Bcl-2相关x蛋白（Bax）、半胱氨酸天冬氨酸蛋白酶-3（caspase-3）]及PI3K信号通路相关蛋白 [PI3K、Akt、磷酸化Akt（p-Akt）、血红素加氧酶-1（HO-1）]含量。
结果 S组心肌组织结构基本正常，C组心肌纤维化且明显损伤，H组心肌纤维损伤得到改善。与H组比较较，P组大鼠心肌损伤程度较为严重。与S组比较，C组、H组和P组心肌含水量、血浆cTnI、LDH、CK-MB和IL-1β、IL-6、TNF-α浓度、心肌组织MDA、MPO浓度、Bax、caspase-3蛋白含量明显升高（P<0.05），SOD浓度、Bcl-2和PI3K、p-Akt、HO-1蛋白含量明显降低（P<0.05）。与C组比较，H组心肌含水量、血浆cTnI、LDH、CK-MB和IL-1β、IL-6、TNF-α浓度、心肌组织MDA、MPO浓度、心肌组织Bax、caspase-3蛋白含量明显降低（P<0.05），心肌组织SOD浓度、Bcl-2和PI3K、p-Akt、HO-1蛋白含量明显升高（P<0.05）。与H组比较，P组心肌含水量、血浆cTnI、LDH、CK-MB和IL-1β、IL-6、TNF-α浓度、心肌组织MDA、MPO浓度、心肌组织Bax、caspase-3蛋白含量明显升高（P<0.05），心肌组织SOD浓度、心肌组织Bcl-2和PI3K、p-Akt、HO-1蛋白含量明显降低（P<0.05）。C组和P组上述指标差异无统计学意义。
结论 HRS减轻CPB致大鼠心肌损伤的机制与激活PI3K/Akt信号通路有关。 |
| 英文摘要: |
Objective To evaluate the role of phosphatidyl inositol 3 kinase / protein kinase B (PI3K / Akt) signaling pathway in HRS-induced reduction of cardiopulmonary bypass (CPB)-caused myocardial injury in rats.
Methods Forty clean-grade adult male SD rats, 10-12 weeks old, weighing 350-400 g were divided into four groups by random number table method (n = 10): sham operation group (group S), CPB group (group C), HRS treatment group (group H) and PI3K inhibitor group (group P). Group S was placed arteriovenous catheter only without CPB and mechanically ventilated for 90 minutes, and after placing arteriovenous catheter normal saline 6 ml/kg was injected through tail vein. CPB mode was established for 60 minutes in other groups. 60 minutes before CPB, the PI3K inhibitor 6 ml/kg (LY294002, 5 μg/ml ) was injected intraperitoneally into their abdomen, 30 minutes before CPB, normal saline 6 ml/kg was injected through the tail vein in group C, HRS 6 ml/kg was injected through tail vein in groups H and P. The corresponding specimens were taken for testing after the CPB was stopped for 2 hours in all four groups. Morphology of the myocardial tissues was observed by Masson staining. The myocardial water content was determined. The myocardial injury markers [cardiac troponin I (cTnI), lactate dehydrogenase (LDH), creatinine kianse-MB (CK-MB)], inflammatory factors [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)] in plasma and oxidative stress factors [malonaldehyde (MDA), myeloperoxidase (MPO), superoxidedimutase (SOD)] concentration levels were detected by ELISA. Apoptosis-related proteins for myocardial cells [B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x protein (Bax), cysteinyl aspartate specific proteinase-3 (caspase-3)] and PI3K signaling pathway related proteins [PI3K, Akt, phosphorylated Akt (p-Akt), heme oxygenase-1 (HO-1)] were detected by Western blot.
Results Masson trichrome staining showed that myocardial tissue structure in group S was basically normal, myocardial fibrosis and seriously injury in group C, HRS treatment in group H improved myocardial fibrosis and injury, myocardial damage in group P was more serious than that in group H . Compared with group S, the myocardial water content, cTnI, LDH, CK-MB and IL-1β, IL-6, TNF-α in plasma, MDA, MPO, Bax, caspase-3 levels were significantly increased (P < 0.05), SOD, Bcl-2 and PI3K, p-Akt, HO-1 levels were significantly decreased in groups C, H, and P (P < 0.05). Compared with group C, the myocardial water content, cTnI, LDH, CK-MB and IL-1β, IL-6, TNF-α in plasma, MDA, MPO, Bax, caspase-3 levels were significantly decreased in group H (P < 0.05), SOD, Bcl-2 and PI3K, p-Akt, HO-1 levels were significantly increased in group H (P < 0.05). Compared with group H, the myocardial water content, cTnI, LDH, CK-MB, IL-1β, IL-6, TNF-α in plasma, MDA, MPO, Bax, caspase-3 levels were significantly increased in group P (P < 0.05), SOD, Bcl-2 and PI3K, p-Akt, HO-1 levels were significantly decreased in group P (P < 0.05). There were no significant differences in the above indexes between the group C and group P.
Conclusion The role of HRS reducing CPB-caused myocardial injury is related to activating the PI3K/Akt signaling pathway in rats. |
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