To Study The Intervention Effect Of Ventilating Lung, Removing Blood Stasis And Resolving Phlegm Theragy On Hypoxic Pulmonary Hypertension Rats’ Pulmonary Vascular Remodeling

Objective:To study the intervention effect of ventilating lung, removing blood stasis and resolving phlegm theragy on hypoxic pulmonary hypertension rats’pulmonary vascular remodeling, and to investigate its mechanismMethods:We utilized the Xue Quanfu’s method to duplicate the modle of hypoxic pulmonary hypertension rat under the condition of normobaric and hypoxia. Fifty sprague-dawley rats, which selected according to clean grade, healthy and the ratio of male to female (1:1), were divided into5groups at random:normal control group, model group, Chinese herbal compound middle dose group, Chinese herbal compound high dose group and fasudil group, with10rats in each group and half male and half female. After one week adaptive breeding, a intervention experiment which treating groups administered with supplemented medicine has been executed. By the way, the general and mortality situation of rats in the test had been recorded, and the whole treatment was lasted for21days. A modified right heart catheterization was taken to assay mPAP and mCAP. Rats were killed, weighed the right ventricle (RV) and left ventricle added with interventricular septum (LV+S), calculated the right ventricle hypertrophy index (RVHI%). Specimens from the same parts of the rats lung tissue were stained and sectioned, then observed themorphological changes of pulmonary artery under the light microscope. Image analysis system was taken to determine the pulmonary artery diameter (ED), the arterial wall thickness (WT), vascular area (TA), lumen area (LA), and to calculate the percentage of the external diameter of the blood vessel wall thickness (WT%), the total area of the blood vessel wall area (WA%) and lumen area to total area (LA%). The structural changes of the pulmonary tube were observed by optical microscope at400times, the total number of vascular, muscular artery, part of the muscular artery, non-muscle blood vessels in small pulmonary arteries of rats in each group were counted under the observation and the proportional fraction of the measured muscularfilm density of the nucleus in the pulmonary artery was calculated.Results:1、The model group rats’s mPAP, RVHI%, WT%, WA%, LA%respective were (30.27±1.47) mmHg,(41.41±3.71)%,(55.23±3.07)%,(83.12±5.90)%,(16.88±1.74)%, and the normal group’s mPAP, RVHI%, WT%, WA%, LA%respective were [(16.14±0.38),(mmHg24.65±1.85)%,(33.41±3.65)%,(54.23±4.61)%,(45.76±3.23)%。The model group were compared with the normal control group, the difference was statistically significant (P<0.05). There was no significant difference between the groups (P>0.05mCAP), the model of hypoxic pulmonary hypertension rat copied successfully.2、Fasudil group, Chinese herbal compound middle dose group, Chinese herbal compound high dose group’s mPAP respective were (18.85±0.65) mmHg,(21.61±0.38) mmHg,(23.25±1.19) mmHg, and Compared with the normal group (16.14±0.38) mmHg. they were increased, the difference was statistically significant (P<0.05); compared with the model group (30.27±1.47) mmHg comparison of decreased, the difference was statistically significant (P<0.05);the fasudil group were Compared with Chinese herbal compound middle dose and high dose of group in rats of mPAP, the traditional Chinese medicine group rats were decreased, the difference was statistically significant (P<0.05); In the traditional Chinese medicine, the high dose group showed no significant change between the two groups of rats with mPAP,, the difference was not statistically significant (P>0.05).3、Fasudil group, middle dose group, high dose group RVHI%respectively were (30.24±1.82)%,(28.19±1.67)%,(27.64±1.55)%, Compared with the normal control group (24.65±1.85)%, they were significantly increased, the difference was statistically significant (P<0.05)。 Compared with the model group (41.41±3.71)%, they were decreased, the difference was statistically significant (P<0.05). And fasudil group, Chinese herbal compound middle dose group, Chinese herbal compound high dose group of three groups were not statistically different between (P>0.05).4、Fasudil group (WT%),(WA%),(LA%) respectively were (38.15±2.96)%,(68.49±4.16)%,(31.50±3.53)%; middle dose group in the traditional Chinese medicine (WT%),(WA%),(LA%) respectively were (43.12±3.61)%,(65.49±4.15)%,(34.51±3.38)%; high dose group (WT%),(WA%),(LA%) respectively were (44.53±3.76)%,(69.90±4.22)%,(30.10±3.37)%; compared with the rats of normal group, HPH model group, fasudil, middle dose group of traditional Chinese medicine, high dose group rats (WT%),(WA%) were increased,(LA%) were decreased, the difference was statistically significant (P<0.05). Fasudil group, middle dose group, high dose group rats WT%, WA%compared with the HPH model group were decreased, LA%increased, the difference was statistically significant (P<0.05). The fasudil group rats than in WT%dose of Chinese medicine group, high dose group rats decreased, the difference was statistically significant (P<0.05), fasudil group rats WA%, LA%and traditional Chinese medicine in middle dose group, high dose group compared with rats did not change significantly, there was no significant difference (P>0.05).5、Compared with the normal group, HPH model group, fasudil group, middle dose group, high dose group of rat pulmonary artery muscle increased, non-muscular arterioles occupying ratio decreased, muscular artery occupying ratio increased, the difference was statistically signify-cant (P<0.05). Compared with the HPH model group, fasudil group, middle dose group, high dose group of rat pulmonary arterial muscularization of non-muscular arterioles reduce, occu-pying ratio increased, muscular artery occupying ratio decreased, the difference was statistical-ly significant (P<0.05). Fasudil group rats compared with traditional Chinese medicine in midd-le dose group, high dose group rats, the proportion of non muscular artery did not change signi-fycantly, the difference was not statistically significant (P>0.05).6、Compared with the normal group rats, pulmonary arteriole dose group rats membrane nucleus density HPH model group, fasudil group, Chinese medicine increased, the difference was statistically significant (P<0.05). Changes of nuclear density high dose group rats of pulmonary arterioles membrane is not obvious, the difference was not statistically significant (P>0.05). Compared with the HPH model group, fasudil group, middle dose group, high dose group rats of pulmonary arterioles membrane nucleus density decreased, the difference was statistically significant (P<0.05).conclusion:Ventilating lung, removing blood stasis and resolving phlegm theragy can effe-ctively reduce the pulmonary artery pressure in hypoxic pulmonary hypertension rats, inhibit or reverse pulmonary vascular remodeling and right ventricular remodeling. It can improve the function of right heart, its mechanism may be the result of joint action of multiple targets, ways.