Zhang Yi-mei, Liu Wen-juan, Shi Yu-zhi, Gao Yu-fei, Wang Li-ling, Chen Ming-xin
Department of Respiratory Medicine, the First Hospital of Harbin Medical University, Harbin 150001, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2008 Jan;31(1):37-41.
To investigate the expressions of Urotensin II (UII) protein and mRNA and its receptor (UT) mRNA of medium and small pulmonary arteries of rats with chronic thromboembolic pulmonary hypertension.
The Wistar rats were injected thrombi through the jugular vein 2 times in 2 weeks and tranexamic acid was injected peritoneally once daily during the experiment to prevent thrombolysis. The mean pulmonary artery pressure (mPAP) was measured using right cardiac atheterzation. The expressions of UII protein in pulmonary arteries were studied by immunohischemistry with a polycolonal antibody. The expressions of UII mRNA and UT mRNA were detected by in situ hybridization using UII and UT oligonuclear probes. The changes of structures in pulmonary vessle were observed, including relative medial thickness of pulmonary artery (PAMT) and vessle wall area/total vessle area (WA/TA).
The mPAP of the 4 weeks to the 12 weeks groups were (19.9 +/- 6.2) mm Hg (1 mm Hg = 0.133 kPa), (23.8 +/- 4.1) mm Hg and (27.4 +/- 5.4) mm Hg, higher than that of the control group (F = 13.75, P < 0.01, respectively). The PAMT of the 4 weeks to the 12 weeks groups were (42.6 +/- 11.16)%, (47.82 +/- 10.02)% and (53.79 +/- 10.41)%, and WA/TA of the 4 weeks to the 12 weeks groups were (22.75 +/- 6.79)%, (25.32 +/- 4.90)% and (27.05 +/- 7.71)%, both changed significantly as compared to the control group (F = 5.52 and 6.61, P < 0.01, respectively; P < 0.05 in 4 weeks group; P < 0.01 in 8 weeks and 12 weeks groups, respectively). The expressions of UIIprotein, UII mRNA and UT mRNA in the 4 weeks to the 12 weeks groups were obviously higher than the control group (F = 30.39, 30.78 and 14.49, P < 0.01, respectively), and their expressions were more marked in the small pulmonary arteries than in medium pulmonary arteries. The expressions of UIIprotein, UII mRNA and UT mRNA were positively correlated with mPAP and PAMT. The pulmonary vascular remodeling was time-dependently aggravated after embolism (r: 0.822, 0.866 and 0.846; 0.675, 0.712 and 0.756, P < 0.01, respectively).
The expressions of UII protein, UII mRNA and UT mRNA of pulmonary arteries in the animal models were higher than those in the control group. These dynamic changes of UII mRNA, UIIprotein and UT mRNA may contribute to the development of pulmonary hypertension and vascular remodeling after pulmonary thromboembolism.
研究慢性血栓栓塞性肺动脉高压大鼠中小肺动脉中尾加压素II(UII)蛋白及mRNA及其受体(UT)mRNA的表达。
Wistar大鼠在2周内通过颈静脉注射血栓2次,实验期间每日腹腔注射氨甲环酸1次以防止血栓溶解。采用右心导管法测量平均肺动脉压(mPAP)。用多克隆抗体通过免疫组织化学研究肺动脉中UII蛋白的表达。用UII和UT寡核苷酸探针通过原位杂交检测UII mRNA和UT mRNA的表达。观察肺血管结构的变化,包括肺动脉相对中膜厚度(PAMT)和血管壁面积/总血管面积(WA/TA)。
4周、8周和12周组的mPAP分别为(19.9±6.2)mmHg(1mmHg = 0.133kPa)、(23.8±4.1)mmHg和(27.4±5.4)mmHg,高于对照组(F = 13.75,P均<0.01)。4周、8周和12周组的PAMT分别为(42.6±11.16)%、(47.82±10.02)%和(53.79±10.41)%,4周、8周和12周组的WA/TA分别为(22.75±6.79)%、(25.32±4.90)%和(27.05±7.71)%,与对照组相比均有显著变化(F分别为5.52和6.61,P均<0.01;4周组P<0.05;8周和12周组P<0.01)。4周、8周和12周组中UII蛋白、UII mRNA和UT mRNA的表达明显高于对照组(F分别为30.39、30.78和14.49,P均<0.01),且其在小肺动脉中的表达比中肺动脉更明显。UII蛋白、UII mRNA和UT mRNA的表达与mPAP和PAMT呈正相关。栓塞后肺血管重塑呈时间依赖性加重(r分别为0.822、0.866和0.846;0.675、0.712和0.756,P均<0.01)。
动物模型中肺动脉UII蛋白、UII mRNA和UT mRNA的表达高于对照组。UII mRNA、UII蛋白和UT mRNA的这些动态变化可能有助于肺动脉血栓栓塞后肺动脉高压和血管重塑的发展。