Li Tong, Zhao Ming-Jing, Han Xiao-Wan, Deng Yue, Zhao Yi-Zhou, Yang Tao, Wang Lei, Wang Bao-Fu, Lu Zi-Wen, Cheng Wen-Kun, Wu Ai-Ming, Lou Li-Xia, Zhao Jiu-Li
Key Laboratory of Chinese Internal Medicine of Ministry of Education and Dongzhimen Hospital, Institute of Cardiovascular Research, Integrated Traditional Chinese and Western Medicine and Blood Research Laboratory, Beijing University of Chinese Medicine, Beijing 100700, China.
the First Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021, China.
Zhongguo Zhong Yao Za Zhi. 2018 Nov;43(21):4305-4310. doi: 10.19540/j.cnki.cjcmm.20180820.004.
The aim of this paper was to study the curative effect of Huotan Jiedu Tongluo (HTJDTL) decoction on a rabbit model with early atherosclerosis (AS),and furtherly to explore whether it could inhibit the BH4/eNOS uncoupling ROS or not. Twenty-four Japanese white rabbits were randomly divided into sham operation group, model group, HTJDTL decoction group and atorvastatin group. Rabbit models with early atherosclerosis were established by high fat diet, nitrogen drying and carotid artery balloon injury. The rabbits were sacrificed at 7th days after balloon injury and several parameters were measured. The pathological morphology of the common carotid artery was observed by HE staining. The blood lipids were detected by peroxidase method. The ratio of vascular eNOS dimer and monomer was measured by Western blot. The ELISA and biochemical technology were respectively used for testing BH4 and ROS levels in serum. The results showed that compared with the sham operation group, the model group had mild stenosis of the common carotid artery lumen, uneven intimal hyperplasia, lipid deposition in the intima and media, and obvious hyperplasia of the adventitia with inflammatory cell infiltration. The HTJDTL decoction could significantly inhibit the intimal hyperplasia compared with the model group, meanwhile, reduce the lipid deposition of the media and the infiltration of the adventitial cells. Compared with the sham operation group, the blood lipids and ROS of the model animals significantly increased, but BH4 and the ratio of eNOS dimer/monomer decreased. Compared with the model group, HTJDTL decoction significantly reduced the TC, ox-LDL and ROS levels, and also up-regulated eNOS dimer/monomer ratio, but it increased BH4 trend without statistical difference. According to the results, it was found that HTJDTL decoction couldsignificantly prevent and improve the vascular remodeling of rabbits model with early atherosclerosis. The mechanism of decoction may largely be related to the inhibition of BH4/eNOS uncoupling and the reduction of oxidative stress.
本文旨在研究化痰解毒通络（HTJDTL）汤对早期动脉粥样硬化（AS）兔模型的疗效，并进一步探讨其是否能抑制四氢生物蝶呤（BH4）/内皮型一氧化氮合酶（eNOS）解偶联产生活性氧（ROS）。将24只日本大耳白兔随机分为假手术组、模型组、HTJDTL汤组和阿托伐他汀组。通过高脂饮食、氮气干燥和颈动脉球囊损伤建立早期动脉粥样硬化兔模型。在球囊损伤后第7天处死兔子并检测多项指标。采用苏木精-伊红（HE）染色观察颈总动脉的病理形态。采用过氧化物酶法检测血脂。通过蛋白质免疫印迹法检测血管eNOS二聚体和单体的比例。分别采用酶联免疫吸附测定（ELISA）法和生化技术检测血清中BH4和ROS水平。结果显示，与假手术组相比，模型组颈总动脉管腔轻度狭窄，内膜增生不均匀，内膜和中膜有脂质沉积，外膜明显增生伴炎症细胞浸润。与模型组相比，HTJDTL汤能显著抑制内膜增生，同时减少中膜脂质沉积和外膜细胞浸润。与假手术组相比，模型动物的血脂和ROS显著升高，但BH4和eNOS二聚体/单体比例降低。与模型组相比，HTJDTL汤显著降低总胆固醇（TC）、氧化型低密度脂蛋白（ox-LDL）和ROS水平，同时上调eNOS二聚体/单体比例，但升高BH4的趋势无统计学差异。根据结果发现，HTJDTL汤能显著预防和改善早期动脉粥样硬化兔模型的血管重塑。该汤的作用机制可能主要与抑制BH4/eNOS解偶联和降低氧化应激有关。
