中介素抑制高肺血流性肺动脉高压大鼠肺组织胶原生成

Intermedin inhibits pulmonary collagen synthesis in rats with pulmonary hypertension induced by high pulmonary blood flow

目的:研究中介素(IMD)对高肺血流性肺动脉高压大鼠肺组织胶原生成和沉积的调节作用及其机制。方法:健康雄性SD大鼠20只,随机分为对照组(n=7)、分流组(n=7)和分流+IMD组(n=6)。对后2组大鼠行腹主动脉-下腔静脉分流术。8周后,对分流+IMD组大鼠,皮下埋微量渗透泵持续给予IMD 1.5μg·kg-1·h-1。继续饲养2周后,比较各组大鼠肺动脉平均压(m PAP)、肺中、小动脉相对中膜厚度(RMT),肺组织羟脯氨酸、Ⅰ和Ⅲ型胶原、骨形成蛋白-2(BMP-2)含量和I、III型前胶原mRNA表达水平。结果:与对照组相比,分流组大鼠m PAP明显上升,肺中、小动脉RMT明显增加,肺组织羟脯氨酸和Ⅰ、Ⅲ型胶原含量明显增多,Ⅰ、Ⅲ型前胶原mRNA表达上调,BMP-2含量明显增多。IMD则使分流大鼠肺动脉压力明显回降,肺血管结构改变缓解,胶原沉积减少,BMP-2含量降低,Ⅰ、Ⅲ型前胶原mRNA表达下调。结论:IMD可通过抑制高肺血流大鼠肺组织胶原生成和沉积,缓解高肺血流性肺动脉高压和肺血管结构重构形成,该作用可能与BMP-2途径有关。

AIM： To explore the regulatory effect of intermedin （IMD） on pulmonary collagen synthesis and ac- cumulation in rats with pulmonary hypertension induced by high pulmonary blood flow. METHODS： Healthy male SD rats （ rt = 20） were randomly divided into control group （ n = 7 ）, shunt group （ n = 7 ） and shunt with IMD group （ n = 6 ）. The shunting of abdominal aorta and inferior vena cava was produced in rats of shunt group and shunt with IMD group. After 8 weeks, IMD was administered into the rats of shunt with IMD group subcutaneously by mini-osmotic pump for 2 weeks. Mean pulmonary artery pressure （ mPAP）, relative medial thickness （RMT） of pulmonary arteries, contents of hydroxyproline, collagen type I and III, bone morphogenetic protein-2 （ BMP-2）, and the mRNA expression of procollagen I and III in lung tissues were measured and compared. RESULTS ： Compared with control group, mPAP and RMT of medium and small pul- monary arteries in the rats of shunt group were significantly increased. Meanwhile, the lung hydroxyproline, collagens I and III and BMP-2 contents, and the mRNA expression of lung procollagen I and III were all significantly increased compared with control group. However, IMD significantly decreased mPAP, alleviated the changes of pulmonary vascular micro-struc- ture, decreased the collagen accumulation and pulmonary tissue homogenate BMP-2 contents, and inhibited the mRNA ex- pression of procollageu I and III in the lung tissue of shunting rats. CONCLUSION： IMD plays a protective role in the de- velopment of pulmonary hypertension and pulmonary vascular structural remodeling induced by high blood flow by inhibiting pulmonary collagen synthesis and accumulation, possibly in association with the BMP-2 pathway.