The Immune Regulation Mechanism Of Intermittent Low Pressure Hypoxia On Rat Pulmonary Hypertension Prevention

Objective: Pulmonary arterial hypertension(PAH) was a kind of disease mainly characteristics of pulmonary artery pressure increase and vascular spasm,endometrial hyperplasia and restructuring.Its main pathological changes was impaired pulmonary vascular endothelial cells and vascular remodeling caused by hyperplasia of smooth muscle cells,histological studies had shown that pulmonary peripheral existing mast cells,macrophages and T lymphocytes,B lymphocytes and dendritic cells,inflammatory cells and the release of chemotactic factor,adhesion molecule and cell factor,eventually making pulmonary vascular endothelial damage and smooth muscle cell proliferation.Proving in the development and incidence of pulmonary hypertension,disorders of the immune system involved. In recent years,a large number of basic research showed that the intermittent low oxygen(IHH) could affect the immune response and the properties of strength,reducing the occurrence and development of autoimmune disease, and enhanced immunity. Intermittent hypoxia including low oxygen and low pressure-low oxygen, often lower oxygen way could be adverse to the body.A large number of studies had shown that intermittent low oxygen environment for tissue hypoxia tolerance for a variety of organs,tissues,and improved the body immunity,are clearly showed the beneficial aspects,could improve the tolerance of ischemia and hypoxia,for cardiac function impaired and arrhythmia caused by ischemia had protective effect, had beneficial effects on the nervous,kidneys,liver,and other important organs,and also had the antihypertensive effect[2].This study aimed to through the pulmonary hypertension animal model, giving IHH processing, using immunohistochemis try and ELISA methods,from the different level of whole animals,in vitro tissue and cell, systematic observed IHH pretreatment effect on pulmonary hypertension, and deeply discussed its immunological mechanisms.Methods:1 To set up the model: 40 SD(Sprague Dawley) rats, bought in laboratory animal center of Hebei medical university, weight 150-200 g,and raised in without pathogens animal room of physiology teaching and research section of Hebei medical university,regularly changing pad and mouse food.Randomly divided them into 4 groups,and 10 in the normal control group,10 of intraperitoneal MCT injection group(60 mg/kg),10 of IHH treatment group, 10 of IHH + MCT group.MCT groups:SD rats by Monocrotaline(Monocrotaline,MCT) to 60 mg/kg dose one-time intraperitoneal injection,to induce rat chronic PAH model,in 14 days after injection with modified PE head end- 50 tube detection of Right ventricular systolic pressure(Right heart systolic pressure, RVSP) and pulmonary artery pressure, the rat model with chronic PAH appraisal.IHH groups: SD rats under low oxygen cabin,accept simulated altitude 5000 meters(PB=525mm Hg,PO2=108.8mm Hg,O2 concentration 11.1%, atmospheric pressure,400 mm Hg) of low pressure low oxygen treatment,6 hours a day,the rest of the time still in the normal oxygen and pressure conditions, continuous 28 d of intermittent hypoxia.IHH + MCT groups: SD rats under low oxygen cabin, accept simulation, 5000 m above sea level(PB=525mm Hg, PO2=108.8 mm Hg,O2 concentration 11.1%, atmospheric pressure, 400 mm Hg), 6h of low oxygen treatment every day, the rest of the time still in the normal oxygen and pressure conditions, used after continuous 28 d of intermittent hypoxia by intraperitoneal injection of MCT to 60mg/kg dose of disposable, rats induced by chronic PAH model, in 14 days after injection with modified PE head end- 50 tube detection of Right ventricular systolic pressure(Right heart systolic pressure, RVSP) and pulmonary artery pressure.2 Pulmonary hyperten sionchanges in rats:Using right cardiac catheterization method to detect rats’ mean pulmonary artery pressure(m PAP).3 Using high fidelity color image analysis system for quantitative analyzing TNF-α and IL-6 expression of lung biopsy.4 Adopting the method of ELISA to detect the levels of serum TNF-α, IL-16.Results:1 The successfully making rat PAH model: MCT intraperitoneal injection group rats’ m PAP was obviously increased(44.26±3.24) mm Hg,compared with controls it had statistically significant difference [16.68±0.78) mm Hg, P<0.01].2 Incidence rate of PAH in IHH+MCT ratswas significantly compared with MCT rats,but there was no significant change of incidence rate of PAH between IHH and CON rats.3 Lung tumor necrosis factor-a(TNF-α) and interleukin-6(IL-6) protein expression changes lung tissue immune-histochemical staining showing, compared with the MCT group,rat lung tissue TNF-α,IL- 6 expression of IHH group significantly decreased(P<0.05);Compared with the Control group, TNF-α,IL- 6 MCT group was obviously increased(P<0.01),IL-6 and TNF-α rose in IHH group, but there was no significant difference with the Control group(P>0.05);Compared with the MCT group,rat lung tissue of the IHH + MCT group had TNF-α, IL-6 expression significantly decreased(P<0.05); Compared to the control group,the IHH + MCT group’s TNF-α,IL-6 expression had no significant difference compared with the control group(P>0.05).4 The serum levels of tumor necrosis factor-a(TNF-α) and interleukin-6(IL-6) protein expression changes compared with the MCT group, rats’ serum in IHH group had TNF-α IL- 6 expression significantly reduced(P<0.05); Compared with the control group,MCT group’s TNF-α, IL- 6 was obviously increased(P<0.01),IHH group’s IL-6 and TNF-α rose,but there was no significant difference with the control group(P>0.05); Compared with the MCT group,the IHH + MCT group’s rats serum TNF-α、IL-6 expression significantly decreased(P<0.05),compared to the control group,the IHH+MCT group’s TNF-α,IL-6 expression had no significant difference compared with the control group(P>0.05).Conclusions:1 Successful preparation of MCT induced PAH model in rats.2 The lung tissue and serum’s TNF-α and IL-6 differences expression may play an important role in the process of the pulmonary hypertension pathogenesis in rats.3 The IHH to MCT induced rats pulmonary hypertension showed obvious inhibitory effect.After IHH pretreatment of rats,the incidence of MCT induced pulmonary hypertension incidence can be decreased obviously.