痰瘀同治方调控PPARγ/NF-κB通路对大鼠动脉粥样硬化斑块内血管新生的影响  

Effect of Tanyu Tongzhi Recipe on Angiogenesis in Atherosclerosis Plaque Rats by Regulating PPARγ/NF-κB Pathways

作　　者：蔡宏文[1] 缪静[1] 周鑫斌[1] 武丽[1] 庄钦 毛威[1] 

机构地区：[1]浙江中医药大学附属第一医院心内科,杭州310006

出　　处：《中国中西医结合杂志》2017年第5期579-583,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：浙江省中医药科研基金项目(No.2013ZA054;No.2016ZA073);浙江省医药卫生研究计划(No.2013KYB186)

摘　　要：目的观察痰瘀同治方对动脉粥样硬化(atherosclerosis,AS)斑块内血管新生的抑制作用,探讨PPARγ/NF-κB信号通路在其过程中的调控机制。方法 50只Wistar大鼠随机分为空白对照组、模型组、罗格列酮组、痰瘀同治低剂量组(TYTZ低组)和痰瘀同治高剂量组(TYTZ高组),每组10只。空白对照组始终喂基础饲料,其余4组采用高脂喂养+维生素D3负荷+球囊损伤动脉内膜建立AS大鼠模型。空白对照组和模型组大鼠每天予生理盐水4 mL灌胃,罗格列酮组大鼠予罗格列酮3 mg/(kg·d)灌胃,TYTZ低组和TYTZ高组大鼠分别予痰瘀同治方生药7.5、30 g/(kg·d)灌胃,各组均持续给药6周。检测各组大鼠血脂(TC、TG、LDL-C)、炎性因子[C反应蛋白(CRP)、IL-1、单核细胞趋化因子-1(MCP-1)]水平;免疫组化CD31染色观察新生血管密度;Western blot法检测主动脉内PPARγ及NF-κB蛋白表达,并对各组PPARγ与NF-κB蛋白表达水平进行相关性分析。结果 (1)与空白对照组比较,模型组TC、CRP、IL-1和MCP-1水平均升高(P<0.05);与模型组比较,TYTZ高组TC和LDL-C水平降低(P<0.05),罗格列酮组TC和TG水平降低(P<0.05),TYTZ高组和罗格列酮组CRP、IL-1和MCP-1水平均降低(P<0.05)。(2)CD31染色结果显示:与空白对照组比较,模型组的新生血管表达最丰富(P<0.05);与模型组比较,各药物干预组的新生血管密度均下降(P<0.05)。(3)与空白对照组比较,模型组PPARγ蛋白表达水平降低(P<0.05),NF-κB蛋白表达水平升高(P<0.05);与模型组比较,罗格列酮组、TYTZ高和TYTZ低组PPARγ蛋白表达水平均升高(P<0.05),NF-κB蛋白表达水平均降低(P<0.05)。各组大鼠主动脉PPARγ与NF-κB蛋白表达水平呈负相关(r=-0.635,P<0.05)。结论痰瘀同治方具有降脂、抗炎和抑制AS斑块内血管新生的作用,PPARγ/NF-κB通路的激活可能是痰瘀同治方抑制斑块内血管新生的作用机制之一。Objective To observe the inhibitory effect of Tanyu Tongzhi Recipe （TYTZR） on plaque angiogenesis, and to observe the regulatory mechanism of PPARγ/NF-κB pathways in its process. Methods Fifty Wistar rats were randomly divided into 5 groups, i.e., the blank control group, the model group, the rosiglitazone group, the low dose TYTZR group, the high dose TYTZR group, 10 in each group. Rats in the blank control group were fed with basic forage, while those in the rest 4 groups were fed with high fat ＋vitamin D3 overload ＋ balloon injury of arterial intima to establish atherosclerosis （AS） rat model. Rats in the blank control and the model group were administered with normal saline （4 mL） by gastro- gavage. Rats in the rosiglitazone group were fed with rosiglitazone at the daily dose of 3 mg/kg by gastrogavage. Rats in low and high dose TYTZR groups were fed with TYTZR crude drug at the daily dose of 7.5 and 30.0 g/kg respectively by gastrogavage. All treatment lasted for 6 successive weeks. Blood lipids （TC, TG, LDL-C） and inflammatory factors E C-reactive protein （CRP）, IL-1, monocyte chemotactic protein-1 （MCP-1） ] were measured. The density of neovessels was observed by immunohistochemical stai- ning CD31. The protein expression levels of PPARγ/and NF-κB in aorta were detected by Western blot. Correlation analyses were performed between protein expression levels of PPARγ/ and NF-κB in each group. Results （1） Compared with the blank control group, the levels of TC, CRP, IL-1, and MCP-1 significantly increased in model group （P 〈0.05）. Compared with the model group, the levels of TC and LDL-C signifi- cantly decreased in the high dose TYTZR group （P 〈0.05） ; the levels of TC and TG significantly decreased in the rosiglitazone group （P 〈0.05） ; expression levels of CRP, IL-1, and MCP-1 significantly decreased in the high dose TYTZR group and the rosiglitazone group （P 〈0.05）. （2） CD31 immunohistochemical staining showed that the expression of angiogen

关 键 词：痰瘀同治方 动脉粥样硬化 PPARγ/NF-κB 通路 新生血管 

分 类 号：R285.5[医药卫生—中药学]