摘要
目的探讨人参皂苷Rb1对川崎病小鼠心肌损伤的治疗作用及其信号通路。方法将5-6周龄BALB/C小鼠随机分为对照组、模型组、阿司匹林组、人参皂苷Rb1低剂量组(50 mg/kg)和高剂量组(100 mg/kg),每组12只。除对照组外,其他各组均间断性腹腔注射10%牛血清白蛋白生理盐水溶液,以诱发川崎病心肌损伤病理模型,共计6 d,每天2次;阿司匹林组、Rb1低剂量组和高剂量组分别在造模后给予相应药物灌胃20 d。苏木精-伊红染色观察心肌组织病理变化;ELISA法检测肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6等炎症因子及心肌肌钙蛋白I水平变化;酶偶联法检测肌酸激酶、肌酸激酶同工酶、乳酸脱氢酶、α-羟丁酸脱氢酶和谷草转氨酶酶活力;Western blot法检测蛋白酪氨酸激酶/信号传导及转录激活蛋白(janus kinase/signal transducer and activator of transcription,JAKs/STATs)信号通路相关蛋白的表达水平。结果Rb1高剂量显著改善了模型组的心肌纤维断裂和撕裂,以及细胞炎性浸润和坏死等症状。ELISA结果显示,和模型组相比,Rb1高剂量可以显著抑制肿瘤坏死因子-α、白细胞介素-6及-1β的高表达,均恢复到对照组水平,且低、高剂量组之间有剂量依赖性(P<0.05)。Rb1高剂量组的肌酸激酶、肌酸激酶同工酶-MB、乳酸脱氢酶、α-羟丁酸脱氢酶和谷草转氨酶五种酶均恢复到对照组水平,而且低、高剂量组之间有剂量依赖性(P<0.05)。同时,和模型组相比,Rb1高剂量组显著下调了肌钙蛋白I的表达水平(P<0.05)。Western blot结果显示,和模型组相比,Rb1高剂量显著上调了p-JAK2/JAK2、p-STAT3/STAT3和B淋巴细胞瘤蛋白-2/β-肌动蛋白(B-cell lymphoma-2/β-actin,Bcl-2/β-actin)的相对表达水平,同时显著下调了裂解半胱天冬氨酸蛋白酶-3/β-肌动蛋白(Cleaved caspase-3/β-actin)的表达水平,而且低、高两个剂量组之间有剂量依赖性(P<0.05)。结论人参皂苷R
Objective To investigate the therapeutic effect and signaling pathway of ginsenoside Rb1 on myocardial injury in mice with Kawasaki disease.Methods BALB/C mice aged 5-6 weeks were randomly divided into control group,model group,aspirin group,ginsenoside Rb1 low dose group(50 mg/kg)and high dose group(100 mg/kg),with 12 mice in each group.Except the control group,other groups were treated with intermittent intraperitoneal injection of 10%bovine serum albumin saline solution to induce Kawasaki disease myocardial injury pathological model with a total of 6 days(twice a day);aspirin group,Rb1 low and high-dose group were given corresponding drugs by gavage for 20 days after modeling.The pathological changes of myocardial tissue were observed by hematoxylin eosin staining.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)and cardiac troponin I(cTnI)in serum and myocardial tissue were detected by ELISA.The activities of creatine kinase(CK),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),α-hydroxybutyrate dehydrogenase(α-HBDH)and aspartate aminotransferase(AST)in serum were detected by enzyme coupling method.The expression levels of janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway related proteins in myocardial tissue were detected by Western blot.Results High dose of Rb1 significantly improved myocardial fiber rupture and tear,inflammatory infiltration and necrosis induced by myocardial injury in model group.ELISA results showed that,compared with the model group,high-dose Rb1 could significantly inhibit the high expression of tumor necrosis factor-α,interleukin-1β,interleukin-6,which were restored to the level of the control group,and there was a dose-dependent relationship between the low and high-dose groups(P<0.05).The results of enzyme coupling method showed that creatine kinase,creatine kinase isoenzyme-MB,lactate dehydrogenase,α-hydroxybutyrate dehydrogenase,and aspartate aminotrasferase in Rb1 high-dose group
作者
齐双辉
张敬莹
肖锋
魏兵
马俊
刘宁
Qi Shuanghui;Zhang Jingying;Xiao Feng;Wei Bing;Ma Jun;Liu Ning(Department of Neonatology,General Hospital of Northern Theater Command,Shenyang 110015,China;Department of Traditional Chinese Medicine Analysis,College of Traditional Chinese Medicine,Shenyang Pharmaceutical University,Shenyang 110016,China)
出处
《中国小儿急救医学》
CAS
2021年第3期209-214,共6页
Chinese Pediatric Emergency Medicine
基金
2018年辽宁省科技计划项目(2018225070)。
关键词
人参皂苷RB1
川崎病
心肌损伤
抗炎
信号通路
Ginsenoside Rb1
Kawasaki disease
Myocardial injury
Anti-inflammatory
Signaling pathway
