摘要目的 观察灯盏花素对低氧大鼠肺动脉压、肺小动脉Rho激酶ROCK Ⅰ和ROCK Ⅱ及Rho激酶mRNA的影响,探讨灯盏花素预防低氧性肺动脉高压的作用和机制.方法 将18只健康雄性SD大鼠分为健康组、低氧组和灯盏花素预防组.以常压低氧法复制肺动脉高压模型,以微导管法测定平均肺动脉压(mPAP).分离大鼠心脏,测量右心室(RV)及左心室加室间隔(LV+S)的重量,以RV/(LV+S)代表右心肥厚指数.应用图像分析技术测定肺小动脉管壁厚度占外径的百分比和管壁面积占总面积的百分比,反映肺血管重塑情况.应用免疫组化法测定肺小动脉Rho激酶蛋白的表达,原位杂交法测定肺小动脉Rho激酶mRNA的表达.结果 低氧组大鼠mPAP为(27.3±5.0)mm Hg(1 mm Hg=0.133 kPa),明显高于健康组的(16.0±0.6)mm Hg(t=6.74,P<0.05),灯盏花素预防组mPAP为(19.83±1.47)mm Hg,明显低于低氧组(t=4.28,P<0.05);低氧组RV/(LV+S)及肺小动脉厚度指数明显高于健康组(t=3.43,P<0.05),灯盏花素预防组低于低氧组(t=2.39,P<0.05);低氧组ROCK Ⅰ和ROCK Ⅱ免疫组织化学阳性染色(1.29±0.08和1.63±0.24)明显高于健康组(1.17±0.09和1.30±0.16),灯盏花素预防组(1.18±0.10和1.30±0.12)明显低于低氧组(t值分别为3.96,5.85,3.90,5.82,均P<0.05);低氧组ROCK Ⅰ mRNA和ROCK Ⅱ mRNA原位杂交阳性染色(分别为1.37±0.13和1.59±0.31)明显高于健康组(1.22±0.09和1.2±10.15),灯盏花素预防组(1.23±0.13和1.22±0.06)明显低于低氧组(t值分别为4.00,6.02,3.94,5.83,均P<0.05).结论 灯盏花素具有明显预防低氧性肺动脉高压和降低Rho激酶及Rho激酶mRNA的作用.

abstractsObjective To observe the effect of breviscapine on the pulmonary artery pressure and the Rho-kinase and Rho-kinase mRNA in pulmonary arterioles of rats treated with hypoxia, and therefore to explore the mechanisms of breviscapine on hypoxic pulmonary hypertension. Methods Eighteen adult male SD rats were randomly divided into 3 groups. One group was exposed to air ( normal group) , the second group was exposed to isobaric hypoxia for 3 weeks ( hypoxie group), and the third group was exposed to hypoxia for 3 weeks and treated with breviscapine ( preventive group). Cardiac catheterization was used to measure the mean pulmonary arterial pressure (mPAP). The heart was isolated, and the right ventricle(RV), left ventricle plus ventrieular septum ( LV + S) were weighed to calculate the ratio RV/( LV + S). The ratio of vascular wall thickness/vascular external diameter ( WT% ) and the ratio of vascular wall area/ total vascular area ( WA% ) were measured by image analysis. The quantity of Rho-kinase and Rho-kinase mRNA in rat pulmonary arterioles were determined by immunohistochemistry and in situ hybridization respectively. Results The mPAP in the preventive group [ (19.83±1.47 ) mm Hg, 1 mm Hg=0.133kPa] was significantly lower than that of the hypoxic group [ (27.3±5.0) mm Hg] ,t=4. 28, P<0.05.The RV/(LV +S) in the preventive group (0. 29±0.03) was significantly lower than that in the hypoxie group (0.3±0.05, t=2.39, P<0.05). The WT% and WA% in the preventive group (25±5 and 45±5, respectively) were significantly lower than those in the hypoxic group (36±12 and 59±13, respectively,t=4.89, 5.89, P<0.05). The positive staining of ROCK Ⅰ and ROCK Ⅱ on pulmonary arterioles in the preventive group (1.18±0.10 and 1.30±0.12, respectively) were significantly lower than those in the hypoxie group (1.29±0.08 and 1.63±0.24, respectively, t=3.90, 5.82, P<0.05). The positive staining of ROCK ⅠmRNA and ROCK Ⅱ mRNA in the preventive group (1.23±0.13 and 1.22±0.06,respectively) were significantly lower than those in the hypoxic group (1.37±0.13 and 1.59±0.31,respectively, t=3.94, 5.83, P<0.05 ). Conclusion Breviscapine was shown to prevent hypoxie pulmonary hypertension and decrease Rho-kinase and Rho-kianse mRNA.