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隐丹参酮调节PI3K/Akt/mTOR信号通路对心肾综合征大鼠心肾功能的保护作用
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| 篇名： | 隐丹参酮调节PI3K/Akt/mTOR信号通路对心肾综合征大鼠心肾功能的保护作用 |
| TITLE： | Protective effects of cryptotanshinone on heart and kidney function in rats with cardiorenal syndrome by regulating PI3K/Akt/mTOR signaling pathway |
| 摘要： | 目的 探究隐丹参酮（CTS）调节磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路对心肾综合征（CRS）大鼠心肾功能的保护作用及机制。方法采用左冠状动脉前降支结扎结合肾急性缺血再灌注损伤的方法建立大鼠CRS模型，并将模型大鼠随机分为CRS模型组（CRS组）、低剂量CTS干预组（CTS-L组）、高剂量CTS干预组（CTS-H组）和高剂量CTS+PI3K激活剂740Y-P组（CTS-H+740Y-P组），每组12只；另设12只大鼠为正常对照组（Normal组），手术但不造模。CTS-L组、CTS-H组大鼠分别灌胃30、60mg/kgCTS，每日1次，连续14d；CTS-H+740Y-P组除灌胃CTS60mg/kg外，还需腹腔注射10mg/kg740Y-P，每日1次，连续14d。末次给药后，检测大鼠心功能指标[左室射血分数（LVEF）、左室收缩末期内径（LVESD）、左室舒张末期内径（LVEDD）、左室短轴缩短率（LVFS）]和肾功能指标[24h尿蛋白、血尿素氮（BUN）、血肌酐（Scr）、脑钠肽（BNP）]水平；观察大鼠心肾组织病理学变化和纤维化情况；检测大鼠心肾组织中PI3K/Akt/mTOR信号通路相关蛋白的表达水平。结果与Normal组比较，CRS组大鼠LVEF、LVFS均显著降低（P＜0.05）；LVESD、LVEDD、24h尿蛋白，血清BUN、Scr、BNP水平，心肾组织胶原染色面积，心肾组织中PI3K、Akt、mTOR蛋白磷酸化水平均显著升高/增大（P＜0.05）；心肌细胞形态肥大、排列紊乱；肾小管结构紊乱、上皮细胞皱缩，存在炎症细胞浸润。与CRS组比较，CTS-L组、CTS-H组大鼠上述指标变化均显著逆转（P＜0.05），心肾功能有所恢复，病理损伤和纤维化程度减轻。PI3K激活剂740Y-P减弱了CTS对CRS大鼠心肾功能的保护作用。结论CTS可保护CRS大鼠的心肾功能，其作用机制可能与抑制PI3K/Akt/mTOR信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the protective effect and mechanism of cryptotanshinone （CTS） on heart and kidney function in rats with cardiorenal syndrome （CRS） by regulating phosphoinositide kinase-3 （PI3K）/protein kinase B （Akt）/ mammalian target of rapamycin （mTOR） signaling pathway. METHODS CRS model of rats was induced by left anterior descending coronary artery ligation combined with acute renal ischemia-reperfusion injury. Model rats were randomly divided into CRS model group （CRS group）， low-dose CTS group （CTS-L）， high-dose CTS group （CTS-H group）， high-dose CTS+PI3K activator 740Y-P group （CTS-H+740Y-P group）， with 12 rats in each group. Another 12 rats were selected as the normal control group （Normal group） and were carried out surgery without modeling. CTS-L group and CTS-H group were respectively given CTS 30 and 60 mg/kg intragastrically， once a day， for consecutive 14 d. Besides the intervention of CTS 60 mg/kg intragastrically， CTS-H+740Y-P group was given 10 mg/kg 740Y-P intraperitoneally， once a day， for 14 consecutive days. After the last medication， the levels of cardiac function [left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， left ventricular fraction shortening （LVFS）] and renal function [24 h urinary protein， blood urea nitrogen （BUN）， serum creatinine （Scr）， brain natriuretic peptide （BNP）] were detected in rats. The pathological changes and fibrosis of the heart and kidney in rats were observed； the expressions of PI3K/Akt/mTOR signaling pathway in heart and renal tissue were all detected. RESULTS Compared with Normal group， the levels of LVEF and LVFS in rats were all decreased significantly in CRS group （P＜0.05）； the levels of LVESD， LVEDD， 24 h urinary protein， serum levels of BUN， Scr and BNP， collagen area and the phosphorylation of PI3K， Akt and mTOR protein in heart and renal tissue were all increased significantly （P＜0.05）. The morphology of myocardial cells was enlarged and disordered； the structure ofrenal tubules was disordered， epithelial cells were wrinkled， and there was infiltration of inflammatory cells. Compared with CRS group， the above indexes of rats were reversed significantly in CTS-L group and CTS-H group （P＜0.05）； heart and kidney function had been restored， and pathological damage and fibrosis had been reduced. PI3K activator 740Y-P weakened the protective effect of CTS on cardiac and renal function in CRS rats. CONCLUSIONS CTS can protect heart and kidney function in CRS rats， the mechanism of which may be associated with inhibiting the PI3K/Akt/mTOR signaling pathway. |
| 期刊： | 2024年第35卷第17期 |
| 作者： | 王心；鲁华；孔露娇；郭晓阳；马亭亭；卢玥 |
| AUTHORS： | WANG Xin，LU Hua，KONG Lujiao，GUO Xiaoyang，MA Tingting，LU Yue |
| 关键字： | 隐丹参酮；PI3K/Akt/mTOR信号通路；心肾综合征；心肾功能 |
| KEYWORDS： | cryptotanshinone； PI3K/Akt/mTOR signaling pathway； cardiorenal syndrome； heart and kidney function |
| 阅读数： | 5 次 |
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