摘要
目的探讨葛根素联合阿托伐他汀对2型糖尿病心肌病大鼠血清脂联素(APN)、炎症因子及心肌纤维化的影响,为2型糖尿病心肌病的临床治疗提供理论依据。方法取10只健康雄性SD大鼠作为正常组,取40只健康雄性SD大鼠采用腹腔注射链脲佐菌素的方法建立2型糖尿病心肌病大鼠模型。将造模成功的30只2型糖尿病心肌病大鼠随机分为模型组、阿托伐他汀组、葛根素联合阿托伐他汀组,每组10只。阿托伐他汀组大鼠给予阿托伐他汀2 mg/kg灌胃,葛根素联合阿托伐他汀组大鼠给予葛根素40 mg/kg腹腔注射及阿托伐他汀2 mg/kg灌胃,模型组大鼠给予等量的生理盐水灌胃,均1次/d,连续8周。末次处理大鼠后第2天处死各组大鼠,取腹主静脉血,采用酶联免疫吸附法检测血清APN及炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平;取心肌组织,分别采用Western blot及RT-PCR法检测心肌组织中赖氨酰氧化酶(LOX)、基质金属蛋白酶2(MMP-2)、核因子-κB(NF-κB)蛋白和mRNA表达水平。结果模型组大鼠血清APN水平明显低于正常组(P<0.05),TNF-α、IL-6水平均明显高于正常组(P均<0.05);阿托伐他汀组和葛根素联合阿托伐他汀组大鼠血清APN水平均明显高于模型组(P均<0.05),且葛根素联合阿托伐他汀组明显高于阿托伐他汀组(P<0.05);阿托伐他汀组和葛根素联合阿托伐他汀组大鼠血清TNF-α、IL-6水平均明显低于模型组(P均<0.05),且葛根素联合阿托伐他汀组均明显低于阿托伐他汀组(P均<0.05)。模型组大鼠心肌组织中LOX、MMP-2、NF-κB蛋白和mRNA表达水平均明显高于正常组(P均<0.05);阿托伐他汀组和葛根素联合阿托伐他汀组大鼠心肌组织LOX、MMP-2、NF-κB蛋白和mRNA表达水平均明显低于模型组(P均<0.05),且葛根素联合阿托伐他汀组均明显低于阿托伐他汀组(P均<0.05)。结论葛根素联合阿托伐他汀可通过明显下调2型糖尿病心肌病大鼠心肌组织中LOX、MMP-2和NF-κB的表达,升高血清APN水平,从而达到抑制心脏重塑、改善心肌纤维化、减轻心肌炎症反应、保护心肌的目的。
Objective It is to study the effects of puerarin combined with atorvastatin on adiponectin(APN),inflammatory factors and myocardial fibrosis in type 2 diabetic cardiomyopathy(DCM)rats,and provide some theoretical evidence for the clinical treatment of type 2 diabetic cardiomyopathy.Methods Ten healthy male SD rats were selected as the normal group,and 40 healthy male SD rats were intraperitoneally injected with streptozotocin to establish models of type 2 diabetic cardiomyopathy.30 successful rat models of type 2 diabetic cardiomyopathy were randomly divided into model group,atorvastatin group,puerarin+atorvastatin group,10 rats in each group.The rats in the atorvastatin group were given atorvastatin 2 mg/kg by gavage,the rats in the puerarin+atorvastatin group were given puerarin 40 mg/kg by intraperitoneal injection and atorvastatin 2 mg/kg by gavage,the rats in the model group were given the same amount of normal saline by gavage,all once/d for 8 weeks.The rats in each group were sacrificed on the second day after the last treatment,and their abdominal aortic vein blood was taken to detect the levels of serum APN and inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)by enzyme linked immunosorbent assay,myocardial tissues was taken to detect the expression levels of protein and mRNA of lysyl oxidase(LOX),matrix metalloproteinase 2(MMP-2),nuclear factor-κB(NF-κB)in myocardial tissue by Western blot and RT-PCR respectively.Results The level of serum APN in the model group was significantly lower than those in the normal group(P<0.05),and the levels of TNF-αand IL-6 were significantly higher than those in the normal group(P<0.05).The level of serum APN in the statastatin group and atorvastatin+puerarin group was significantly higher than that in the model group(P<0.05),and the puerarin+atorvastatin group was significantly higher than that in the atorvastatin group(P<0.05).The level of serum serum TNF-αand IL-6 in the statastatin group and atorvastatin+puerarin group was significantly lower than that in the model group(P<0.05),and the puerarin+atorvastatin group was significantly lower than that in the atorvastatin group(P<0.05).The expression levels of LOX,MMP-2,NF-κB protein and mRNA in myocardial tissue of the rats in model group were significantly higher than those in normal group(P<0.05);The expression levels of LOX,MMP-2,NF-κB protein and mRNA in myocardial tissue of the rats in statastatin group and atorvastatin+puerarin group were significantly lower than those in model group(P<0.05),and the puerarin+atorvastatin group were significantly lower than those in the atorvastatin group(P<0.05).Conclusion Puerarin combined with atorvastatin can significantly reduce the expression of LOX,MMP-2 and NF-κB in the myocardial tissue,increase serum APN levels of type 2 diabetic cardiomyopathy rats,thereby reach the purpose of inhibiting heart remodeling,improving myocardial fibrosis,relieve myocardial inflammation and protecting myocardium.
作者
张驰
王珣
王丽岳
徐莉
徐超
赵生娣
管倩倩
ZHANG Chi;WANG Xun;WANG Liyue;XU Li;XU Chao;ZHAO Shengdi;GUAN Qianqian(Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 430081, Hubei,China;Wuhan Third Hospital, Wuhan 430060, Hubei,China)
出处
《现代中西医结合杂志》
CAS
2020年第11期1167-1171,1207,共6页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
武汉市卫生局临床医学科研项目(WX12D01)。
关键词
糖尿病心肌病
葛根素
阿托伐他汀
大鼠
心肌纤维化
炎症因子
脂联素
type 2 diabetic cardiomyopathy
puerarin
atorvastatin
rat
myocardial fibrosis
inflammatory factor
adiponectin
作者简介
张驰,男,硕士,主治医师,擅长冠心病相关疾病的诊治;通信作者:王珣,E-mailzc19820911@163.com。
