姜黄素改善慢性肺动脉高压肺血管重塑作用途径的研究

Study on the mechanism of how curcumin improves pulmonary vascular remodeling associated with chronic pulmonary arterial hypertension

目的：探究姜黄素改善慢性低O2高CO2大鼠肺动脉高压肺血管重塑作用途径的研究。方法：建立慢低O2高CO2肺血管重塑模型，以24只雄性大鼠为受试对象，随机分为四组（n=6）：I组（常氧空白对照组），Ⅱ（低O2高CO2模型组），Ⅲ组（色甘酸钠对照组），Ⅳ组（姜黄素实验组）。将后3组动物放入常压低O2高CO2舱中，吸入O2浓度8％～11％，CO2浓度3％～5％，每天8h，每周6d，连续4周，Ⅲ组给予色甘酸钠以20mg／kg体重腹注射处理，Ⅳ组给予姜黄素混悬液按150mg/kg体重灌胃处理。光镜下、透射电镜下观察肺动脉血管壁及其周围大细胞超微结构形态学改变，甲苯胺蓝染色法和免疫组织化学法对肺动脉周围的肥大细胞及其脱颗粒状态进行性定量测定。结果：①电镜下，Ⅱ组肺细小动脉中膜平滑肌增生，外膜胶原纤维密集，内弹力板扭曲，内皮细胞起，血管外肥大细胞内颗粒减少，胞膜不完整；光镜下，Ⅱ组相比1组肺细小动脉管腔／管总面积（WA／TA）明显升（P〈0．05）、管腔／管总面积（EA／TA）明显降低（P〈0．05），甲苯胺蓝染色肥大细胞细胞数（NMC）、肥大细胞脱颗率（DR）及免疫组化检测类胰蛋白酶阳性细胞数（TBS）高于I组（P〈0．05）；②干预后，电镜下，Ⅲ组、Ⅳ组血管结基本正常，平滑肌增生及胶原增生较Ⅱ组轻，肥大细胞膜完整；光镜下，两干预组相比Ⅱ组WA／TA明显降低（P〈0．05）、ET／TA明显升高（P〈0．05），甲苯胺蓝染色NMC、DR、TBS阳性细胞数分别低于Ⅱ组（P〈0．05）。结论：姜素可通过Mc途径抑制慢性低O2高CO2导致的大鼠肺血管重塑改变。

Objective： To investigate the mechanism of how curcumin improves pulmonary vascular remodeling associated with chronic pul- monary arterial hypertension. Methods： The model of chromic hypoxia hypercapniapulmoary remodeling was made. Twenty-four male rats were randomly divided into 4 groups （ n = 6 ） ： group I （normoxia control group ）, group Ⅱ （hypxia and hypercapnia model group） ,group III （disodi- urn cmmoglycate control group）,group IV （curcumin treated group）. The last 3 group rats were put in a hypoxia cabin where the concentrate of O2 was 8 % ～ 11% and the concentrate of CO2 was 3 % ～ 5 %, for 8 h a day and lasting 4 w in total. Group Ⅲ rats were intraperitoneally injected with disodium cromoglycate （20 mg/kg） and group IV rats were administrated with curcumin by garage （150 mg/kg）. The morpho- logical changes of pulmonary vessel walls and the ultrastructure of mast ceils were observed by the optics microscope and the transmission elec- tron microscope. Mast cells and its degranulation state were measured by toluidine blue staining and immunohistochemistry. Data were ex- pressed as means±SD （standard deviation） and analyzed with SPSS17.0 software. Results： ① By optics microscopy observation, the value of WA/TA was significantly higher in U group than other groups（ P 〈 0.05）. ② Electron microscope showed that the endothelial cells of pul- monary arterioles in Ⅲ and IV group were near to I group and the proliferation of pulmonary arterial media smooth ceil layer and collagen fibers in adventitia was much lighter than those in II group . The membrane of mast cells was more intact in Ⅰ, Ⅲ, IV group than ② group. ③ The number of mast cells, the degranlation rate of master ceils and the number of positive tryptase stained cells in II group were significantly more than those in other groups. （ P 〈 0.05）. Condusion： Curcumin may inhibit the remodeling of pulmonary vessel induced by chronic hypoxia hypereapnia by mast cell regulation.