p38MAPK抑制剂CBS3830对糖尿病大鼠自体静脉移植内膜增生的影响及机制探讨

Effect and mechanism of p38MAPK inhibitor CBS3830 on intimal hyperplasia in autogenous vein grafts of diabetic rats

目的观察p38MAPK抑制剂CBS3830对糖尿病大鼠自体移植静脉内膜增生的影响,并探讨机制。方法 SD雄性大鼠30只,采用腹腔注射链脲佐菌素法建立糖尿病动物模型;将造模成功的26只随机分为两组,采用改良cuff法建立自体静脉移植模型,造模前1 h药物组经胃管灌入0.3 mg/ml的CBS3830 10 ml/kg,对照组同法给予等体积的CBS3830溶媒1%甲基纤维素。分别于术前及术后1、3、7 d采用ELSIA法检测大鼠血清TNF-α;于第7天处死动物并获取移植静脉标本,HE染色观察大鼠移植静脉内膜及中膜厚度。结果术后7 d,药物组大鼠血清TNF-α水平显著低于对照组(P<0.05),药物组内膜增生程度明显低于对照组。药物组内膜厚度为(33.6±1.34)μm、内膜厚度/中膜厚度为1.23±0.08,对照组分别为(38.5±1.50)μm、1.7±0.12,两组相比,P均<0.05。结论 p38MAPK抑制剂CBS3830对糖尿病大鼠自体移植静脉内膜的增生有抑制作用,可能与其降低血清TNF-α水平有关。

Objective To investigate the role and mechanism of p38MAPK inhibitor CBS3830 on intimal hyperplasia in autogenous vein graft of diabetic rats.Methods Diabetic rat model were established by intraperitoneal injection of streptozotocin（STZ） in 30 male Sprague-Dawley rats.Autogenous vein graft model was established with the improved cuff technique in the 26 diabetic rats which were divided into drug group and control group.One hour before modeling,CBS3830 of 0.3mg/ml concentration was poured into the drug group rats through stomach tube,the dose was 10 ml/kg.As for the control group was given the same volume of 1% methylcellulose works as the solvents for CBS3830.Blood samples were harvested at day 1,day 3,day 7 after surgery and before surgery.Vein graft samples were harvested day 7 after surgery for histological examination.ELSIA was used to detect the serum levels of TNF-α.HE staining was used to detect the pathological changes of vascular intima and media each group.Results The serum levels of TNF-α of drug group was significantly lower than control group at 7 days after surgery.The degree of internal membrane proliferation and Intima-media thickness ratio of drug group[（33.6±1.34）μm,1.23±0.08]was significantly lower than control group[（38.5±1.50）μm,1.7±0.12],P0.05.Conclusion p38MAPK inhibitor CBS3830 has a significant anti-proliferative effect in autogenous vein graft of diabetic rats,which may be related to reducing the serum level of TNF-α.