柴白温胆汤对动脉粥样硬化大鼠内皮功能及MMP-9/TIMP-1的影响

Effects of Chaibai Wendan Decoction on Endothelial Function and Matrix Metalloproteinase 9/Tissue Inhibitor of Metalloproteinase 1 in Rats with Atherosclerosis

【目的】探讨柴白温胆汤对动脉粥样硬化大鼠内皮功能及MMP-9/TIMP-1的影响。【方法】将45只大鼠分为正常组(N=10)、造模组(N=35)。采用维生素D3腹腔注射联合高脂喂养方法建立AS模型(时间为8周)。造模结束后,从造模组抽取5只大鼠取腹主动脉组织进行光镜和电镜检查以判断造模是否成功,再将剩余的30只大鼠随机分为模型组、他汀组、柴白温胆汤组,每组10只。他汀组给予阿托伐他汀钙片(剂量为0.6 mg·kg-1·d-1)灌胃,柴白温胆汤组给予柴白温胆汤(剂量为16 g·kg-1·d-1)灌胃,正常组和模型组每天给予等体积的生理盐水进行灌胃。共给药4周。给药结束后,采用酶联免疫吸附分析(ELISA)检测各组大鼠血清一氧化氮(NO)、内皮素1(ET-1),血栓素B2(TXB2)、6-酮-前列腺素F1α(6-keto-PGF1α)、基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制因子1(TIMP-1)的水平。【结果】本研究成功复制动脉粥样硬化大鼠模型。与正常组比较,模型组大鼠血清ET-1、TXB2、MMP-9水平明显升高(P <0.05),NO、6-keto-PGF1α、TIMP-1水平明显降低(P <0.05);与模型组比较,柴白温胆汤组大鼠血清ET-1、TXB2、MMP-9水平明显降低(P <0.05),NO、6-keto-PGF1α、TIMP-1水平明显升高(P <0.05)。【结论】柴白温胆汤可调控动脉粥样硬化大鼠内皮功能及MMP-9/TIMP-1的平衡。

Objective To investigate the effects of Chaibai Wendan Decoction(CWD)on the endothelial functionand matrix metalloproteinase 9/tissue inhibitor of metalloproteinase 1(MMP-9/TIMP-1)in rats with atherosclerosis.Methods Forty-five rats were randomly divided into normal group(N = 10)and modeling group(N = 35). The 35 rats in the modeling group were given intraperitoneal injection of vitamin D3 combined with high fat feeding for 8weeks to induce into atherosclerosis. After modeling,the aorta abdominalis tissues from 5 model rats were used forlight microscopic and electron microscopic examination to judge the successful establishment of the model. Andthen the model rats were randomly divided into model group,Atorvastatin group and CWD group,10 rats in each group. Atorvastatin group was given intragastric administration of atorvastatin calcium tablets at the dosage of0.6 mg·kg-1·d-1,CWD group was given intragastric administration of CWD at the dosage of 16 g·kg-1·d-1,and thenormal group and model group were given the same volume of normal saline. The treatment lasted for 4 weeks. Aftertreatment,the serum levels of nitric oxide(NO),endothelin 1(ET-1),thromboxane B2(TXB2),6-keto-prostaglandin F1α(6-keto-PGF1α), matrix metalloproteinase 9(MMP-9), and tissue inhibitor ofmetalloproteinase 1(TIMP-1)in various groups were measured by enzyme-linked immunosorbent assay(ELISA).Results Compared with the normal group, the serum levels of ET-1, TXB2 and MMP-9 were increasedsignificantly(P < 0.05),and the serum levels of NO,6-keto-PGF1α and TIMP-1 were decreased in the modelgroup(P < 0.05). Compared with the model group,ET-1,TXB2 and MMP-9 were decreased significantly(P <0.05),and NO,6-keto-PGF1α and TIMP-1 were increased in the CWD group(P < 0.05). Conclusion CWD haseffects on regulating the endothelial function and the balance of MMP-9/TIMP-1 in atherosclerosis rats.