科罗索酸增强右美托咪定对链尿佐菌素诱导的糖尿病大鼠心肌氧化应激和凋亡的保护作用

目的:探究科罗索酸对右美托咪定抗链尿佐菌素(STZ)诱导糖尿病大鼠心肌氧化应激和心肌细胞凋亡作用的影响。方法:将60 只雄性SD 大鼠随机分为对照(Ctrl)组、STZ 组,科罗索酸(CA)组、右美托咪定(DEX)组和CA+DEX 组,除Ctrl 组外,其余组大鼠腹腔注射STZ(60 mg/ kg)诱导糖尿病大鼠模型。模型复制成功后分别给予DEX (20 μg/ kg)和CA (20 mg/ kg),7 d 后处死大鼠,HE 染色检测心肌损伤情况,试剂盒检测血清肌红蛋白(Mb)、肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)、超氧化物歧化酶(SOD)和丙二醛(MDA) 的浓度;Western blot 检测Ki67 和Caspase-3 的表达;ELISA 检测血清肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)的含量。结果:与Ctrl 组比较,STZ 组大鼠心肌组织损伤加重;与STZ 组比较,DEX 组大鼠心肌损伤有所减轻,CA 组效果甚微;但CA+DEX 组大鼠心肌损伤明显轻于DEX 组;同时,DEX 能显著降低模型大鼠血清Mb、CK-MB 和cTnI 浓度,并能升高血清SOD 浓度、降低MDA 浓度,CA 效果较弱,但CA 能显著增强DEX 对Mb、CK-MB、CTNI、SOD 和MDA 分泌的调控作用;此外,与STZ 组比较,DEX 组大鼠Ki67 表达明显上调,Caspase-3 表达明显减少,CA 对Ki67 和Caspase-3 的调控作用较弱,但能显著增强DEX 对Ki67 和Caspase-3 表达的调控作用。DEX 还能显著抑制炎症因子TNF-α和IL-6 的分泌,CA 能增强DEX 对TNF-α和IL-6 分泌的抑制作用。结论:CA 能增强DEX 对STZ 诱导的糖尿病大鼠心肌氧化应激和心肌细胞凋亡的抑制作用。

Corosolic acid strengthens protective effect of dexmedetomidine on oxidative stress and apoptosis of myocardium in STZ-induced diabetic rats

Objective:To investigate the effect of corosolic acid on inhibitory effects of dexmedetomidine on oxidative stress and cell apoptosis of myocardium in diabetic rats.Methods:60 SD rats were divided into control (Ctrl),streptozotocin (STZ),corosolic acid (CA),dexmedetomidine (DEX) and CA+DEX group,and intraperitoneally injected with STZ(60 mg/ kg) except Ctrl group.Rats in CA,DEX and CA+DEX group were treated with DEX (20 μg/ kg) and CA (20 mg/ kg).7 d after CA and DEX injection,rats were sacrificed and HE staining was performed for the injury of myocardium.The concentrations of myoglobin (Mb),creatine kinase MB (CK-MB),cardiac troponin I (cTnI),superoxide dismutase (SOD) and malondialdehyde (MDA) in serum was measured by kits.The expressions of Ki67 and Caspase-3 were determined by Western blot and the concentrations of tumor necrosis factor-α(TNF-α) and IL-6 were measured by ELISA assay.Results:Compared with Ctrl group,the injury of myocardium was aggravated in STZ group,the injury was alleviated in DEX group,but alleviative effect was very slight in CA group,and the injury in CA +DEX group was milder than DEX group.Meanwhile,DEX decreased the concentrations of Mb,CK-MB and cTnI significantly,and up-regulated the concentration of SOD and down-regulated MDA.But the improvements of CA were very mild.CA enhanced the effects of DEX on Mb,CK-MB,CTNI,SOD and MDA;in addition,compared with STZ group,the protein levels of Ki67 and Caspase-3 were increased and decreased respectively DEX group.The effects of CA were more weakness but strengthened the regulatory effects of DEX on expressions of Ki67 and Caspase-3 Notably.Furthermore,DEX inhibited secretion of TNF-αand IL-6,CA enhanced effects of DEX on TNF-αand IL-6.Conclusion:CA strengthens the inhibitory effects of DEX on oxidative stress and apoptosis of myocardium in STZ-induced diabetic rats.