姜黄素和/或有氧运动改善高脂血症大鼠心肌细胞焦亡的作用机制

毛永强; 周绮云; 张馨月; 杨洪志

doi:10.13386/j.issn1002-0306.2021050182

姜黄素和/或有氧运动改善高脂血症大鼠心肌细胞焦亡的作用机制

Mechanism of Curcumin and/or Aerobic Exercise Improving Pyroptosis in Myocardium of Hyperlipidemic Rats

摘要

摘要: 研究姜黄素和/或有氧运动改善高脂血症大鼠心肌细胞焦亡的作用机制。50只5周龄雄性SD大鼠随机分为普通膳食+安静组（RDC组）、高脂膳食+安静组（HDC组）、高脂膳食+有氧运动组（HDM组）、高脂膳食+姜黄素+安静组（HDCC组）和高脂膳食+姜黄素+有氧运动组（HDCM），每组10只。第3周起，HDCC、HDCM组以400 g/（kg·d）姜黄素灌胃，其余组以等体积0.5%羧甲基纤维素钠灌胃；HDM、HDCM组进行有氧运动干预，其他组无任何运动干预。6周干预结束后24 h，观察各组大鼠心脏组织形态，检测血液、心肌组织相关生化指标。结果显示：血清总胆固醇（TC）、甘油三脂（TG）、低密度脂蛋白胆固醇（LDL-C），HDC组较RDC组均显著升高（P<0.01）；血清TC、TG，HDCC、HDM、HDCM组较HDC组均显著降低（P<0.01）；血清TC，HDCM组较HDCC、HDM显著降低（P<0.05或P<0.01）；血清LDL-C，HDCC组、HDCM组较HDC组显著降低（P<0.05或P<0.01），HDCM组较HDCC组、HDM组均显著降低（P<0.05或P<0.01）。血清高密度脂蛋白胆固醇（HDL-C）水平，HDC组较RDC组显著降低（P<0.05）；HDCC、HDM、HDCM组较HDC组均显著升高（P<0.05或P<0.01）；HDCM组较HDM组均显著升高（P<0.01）。RDC组心肌形态正常，HDC组出现炎性损伤；HDCC、HDM、HDCM组较HDC组明显改善，其中HDCM组最为显著。心肌白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）含量，HDC组较RDC组均显著升高（P<0.01）；HDCC、HDM、HDCM组较HDC组均显著降低（P<0.01）；HDCC、HDM组较HDCM组显著升高（P<0.05或P<0.01）。心肌损伤标志物肌酸激酶同工酶MB型（CK-MB），HDC组较RDC组均显著升高（P<0.01）；HDCC、HDM、HDCM组较HDC组均显著降低（P<0.01）；HDCM组较HDCC、HDM显著降低（P<0.01）。心肌NOD样受体蛋白3（NLRP3）、凋亡相关斑点样蛋白（ASC）、含半胱氨酸的天冬氨酸蛋白水解酶1（Caspase1）蛋白质表达（H-score），HDC组显著高于RDC组（P<0.01）；HDCC组、HDM组、HDCM组显著低于HDC组（P<0.05或P<0.01）；HDCC组、HDM组显著高于HDCM组（P<0.05或P<0.01）。从而说明，为期6周的姜黄素和/或有氧运动干预可以改善高脂血症大鼠心肌细胞焦亡，抑制过度炎症反应，保护心脏功能/结构，其机制可能与抑制NLRP3/Caspase1通路活化相关。二者联合干预效果最佳。

Abstract: To study the mechanism of curcumin and/or aerobic exercise improving pyroptosis in myocardium of hyperlipidemic rats. Fifty 5-week-old male SD rats were randomly divided into normal diet control group (RDC), high fat diet control group (HDC), high fat diet with curcumin group (HDCC), high fat diet with aerobic exercise group (HDM), high fat diet with curcumin and aerobic exercise group (HDCM), ten in each group. From the third week, group HDCC and HDCM were injected intragastrically with curcumin at 400 g/(kg·d), and the other groups were given an equal volume of 0.5% sodium carboxymethylcellulose. Group HDM and HDCM performed aerobic exercise intervention, and the other groups did not. Twenty-four hours after the end of 6-week-intervention, the myocardial microstructure in each group was observed, blood and myocardium related biochemical indicators were tested. The results showed that, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), HDC were significantly higher than RDC (P<0.01). Serum TC and TG, HDCC, HDM and HDCM were significantly lower than HDC (P<0.01). Serum TC, HDCM decreased significantly compared with HDCC and HDM (P<0.05 or P<0.01). Serum LDL-C, HDCC and HDCM were significantly lower than HDC (P<0.05 or P<0.01), HDCM was significantly lower than HDCC and HDM (P<0.05 or P<0.01). Serum high-density lipoprotein cholesterol (HDL-C), HDC was significantly lower than RDC (P<0.05), HDCC, HDM and HDCM significantly were higher than HDC (P<0.05 or P<0.01), HDCM was significantly higher than HDM (P<0.01). The myocardial microstructure of RDC was normal, there were inflammatory injury in myocardium of HDC, injury in HDCC, HDM, HDCM were improved significantly, and HDCM was the most significant in the three. Myocardial interleukin-1β (IL-1β) and interleukin-18 (IL-18), HDC was significantly higher than RDC (P<0.01), HDCC, HDM and HDCM were significantly lower than HDC group (P<0.01), HDCC and HDM were significantly higher than HDCM (P<0.05 or P<0.01). Myocardial injury marker creatine kinase-MB (CK-MB), HDC was significantly higher than RDC (P<0.01), HDCC, HDM and HDCM were significantly lower than HDC (P<0.01), HDCM was significantly lower than HDCC and HDM (P<0.01). The H-score of myocardial NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and cysteinyl aspartate specific proteinase 1 (Caspase1), HDC was significantly lower than RDC (P<0.01), HDCC, HDM and HDCM were significantly higher than HDC (P<0.05 or P<0.01), HDCC and HDM were significantly lower than HDCM (P<0.05 or P<0.01). Therefore, the 6-week curcumin and/or aerobic exercise intervention could improve pyroptosis in myocardium of hyperlipidemic rats, inhibit excessive inflammatory response, and protect the heart function/structure, which might be related to inhibiting NLRP3/Caspase1 pathway. The effect of combined intervention was better.