本文關(guān)鍵詞：間歇性低壓低氧對(duì)大鼠肺動(dòng)脈高壓的預(yù)防作用及血管保護(hù)機(jī)制　出處：《河北醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 間歇性低壓低氧 肺動(dòng)脈高壓 野百合堿 平均肺動(dòng)脈壓 苯腎上腺素 乙酰膽堿 硝普鈉

【摘要】：目的:近年來人們逐漸認(rèn)識(shí)到,高原上長(zhǎng)期低氧的環(huán)境可增加心臟對(duì)缺血損傷的抵抗力。然而,長(zhǎng)期慢性的持續(xù)性高原低氧又對(duì)機(jī)體有很多不利的作用,如右心室肥厚及紅細(xì)胞增多癥。大量研究表明,間歇性低壓低氧(Intermittent Hypopiesia Hy Poxia,IHH)除具有慢性持續(xù)性低氧的心臟保護(hù)作用外,對(duì)機(jī)體的不良影響也非常低,同時(shí),間歇性低壓低氧又是臨床低氧的常見形式,如冠心病、睡眠呼吸暫停綜合癥。因此,IHH日益受到人們的關(guān)注。已有研究表明,IHH對(duì)機(jī)體有很多益處,例如可保護(hù)神經(jīng)及肝臟等器官組織,對(duì)慢性阻塞性支氣管炎及支氣管哮喘有一定輔助治療作用,也有文獻(xiàn)報(bào)道IHH可對(duì)抗缺血/再灌注所致心功能損傷及心律失常,增強(qiáng)機(jī)體對(duì)缺血、缺氧的耐受性,但未見對(duì)肺動(dòng)脈高壓具有預(yù)防及保護(hù)作用的研究報(bào)道。本實(shí)驗(yàn)采用野百合堿(monocrotaline,MCT)誘導(dǎo)雄性SD大鼠肺動(dòng)脈高壓模型,觀察IHH對(duì)動(dòng)物模型肺組織及肺血管功能學(xué)、形態(tài)學(xué)的作用,并初步探討其對(duì)肺血管的保護(hù)機(jī)制,為臨床治療PAH提供新的實(shí)驗(yàn)及理論依據(jù)。方法:由河北醫(yī)科大學(xué)動(dòng)物實(shí)驗(yàn)研究中心提供的清潔級(jí)健康雄性SD大鼠40只,質(zhì)量(150-200)g,隨機(jī)分為4組,即正常對(duì)照組(CON組)、肺動(dòng)脈高壓組(PAH組)、間歇性低壓低氧處理組(IHH組)、IHH+MCT組。CON組的大鼠不進(jìn)行任何處理,正常飼養(yǎng)28天后直接進(jìn)行右心室收縮壓(right heart systolic pressure,RVSP)和平均肺動(dòng)脈壓力(mean pulmonary artery pressure,m PAP)的測(cè)定,計(jì)算右心室肥厚指數(shù)(right ventricular hypertrophy index,RVHI)并行血管環(huán)灌流實(shí)驗(yàn)觀察血管反應(yīng)性的改變。PAH組經(jīng)腹腔注射MCT14天后測(cè)RVSP及m PAP,計(jì)算RVHI并觀察血管反應(yīng)性的改變。IHH組接受模擬5km海拔高度,每天6h的間歇性低壓低氧處理28d后檢測(cè)RVSP、m PAP,計(jì)算RVHI并觀察血管反應(yīng)性的改變。IHH+MCT組先經(jīng)受28d的IHH后腹腔注射MCT,14天后檢測(cè)RVSP、m PAP,計(jì)算RVHI并觀察血管反應(yīng)性的改變。所有實(shí)驗(yàn)數(shù)據(jù)均采用SPSS 13.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,實(shí)驗(yàn)結(jié)果均為服從正態(tài)分布的計(jì)量資料,結(jié)果以均數(shù)±標(biāo)準(zhǔn)差表示。四組數(shù)據(jù)之間的比較運(yùn)用單因素方差分析(One-way ANOVA),檢驗(yàn)水準(zhǔn)α=0.05,P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1實(shí)驗(yàn)動(dòng)物的死亡情況與一般生長(zhǎng)狀況1.1死亡情況PAH組死亡2只大鼠,其余各組大鼠均全部存活。1.2一般生長(zhǎng)情況PAH組大鼠從腹腔注射MCT后第2周開始體重較CON組減輕,活動(dòng)量也明顯減少,倦臥,喘促,進(jìn)食量減少。IHH組大鼠的活動(dòng)度、進(jìn)食狀況及重量均較同期的PAH組有所改善,但較CON組差。大鼠開胸后肉眼可見PAH組大鼠的右心室明顯增厚,肺部淤血腫脹,部分伴有胸水、腹水,甚至心包積液。2血流動(dòng)力學(xué)結(jié)果2.1各組大鼠m PAP的結(jié)果PAH組的m PAP明顯高于其他三組,差異均有統(tǒng)計(jì)學(xué)意義;IHH+MCT組大鼠的m PAP較PAH組顯著降低,差異有統(tǒng)計(jì)學(xué)意義(IHH+MCT:19.45±1.03 vs PAH:35.28±0.94mm Hg,P0.05);其較CON組的壓力水平偏高,但無統(tǒng)計(jì)學(xué)差異(IHH+MCT:19.45±1.03 vs CON:16.42±0.46mm Hg,P0.05);IHH組的m PAP與CON組相比稍偏高,但無統(tǒng)計(jì)學(xué)意義(IHH:17.86±0.42 vs CON:16.42±0.46mm Hg,P0.05)。2.2各組大鼠RVSP的結(jié)果PAH組的RVSP明顯高于其他三組,差異均有統(tǒng)計(jì)學(xué)意義(PAH:45.14±0.62 vs CON:24.46±1.21mm Hg,P0.05);IHH+MCT組較PAH組顯著降低,差異有統(tǒng)計(jì)學(xué)意義(IHH+MCT:27.58±0.98 vs PAH:45.14±0.62mm Hg,P0.05),其與CON組的壓力水平相比偏高,但無統(tǒng)計(jì)學(xué)意義(IHH+MCT:27.58±0.98 vs CON:24.46±1.21mm Hg,P0.05)。IHH組與CON組相比偏高,但無統(tǒng)計(jì)學(xué)意義(IHH:25.74±1.16 vs CON:24.46±1.21mm Hg,P0.05)。3右心室肥厚指數(shù)(RVHI)的計(jì)算PAH組的RVHI明顯高于其他三組;與CON相比,野百合堿注射后2周,PAH組大鼠的RVHI明顯升高(PAH:48.76±11.7 vs CON:24.43±3.79,P0.05)。IHH+MCT組大鼠的RVHI較PAH組顯著降低,差異有統(tǒng)計(jì)學(xué)意義(IHH+MCT:25.61±4.18 vs PAH:48.76±11.7,P0.05);其與CON組的壓力水平相比偏高,但尚未達(dá)到CON組的壓力水平,差異無統(tǒng)計(jì)學(xué)意義(IHH+MCT:25.61±4.18 vs CON:24.43±3.79,P0.05);IHH組的RVHI與CON組相比偏高,但無統(tǒng)計(jì)學(xué)意義(IHH:27.66±4.17vs CON:24.43±3.79,P0.05)。4低壓低氧對(duì)肺動(dòng)脈內(nèi)皮功能的作用在四個(gè)實(shí)驗(yàn)組中,苯腎上腺素Phenylephrine(PHE)從10-8mol/L到10-5mol/L均可引起血管的內(nèi)皮依賴性收縮反應(yīng),乙酰膽堿Acetylcholine(ACH)從10-8mol/L到10-5mol/L都可引起血管的內(nèi)皮依賴性舒張反應(yīng),硝普鈉Sodium nitropmsside(SNP)從10-8mol/L到10-5mol/L均可引起血管的非內(nèi)皮依賴性舒張反應(yīng),且以上實(shí)驗(yàn)藥物對(duì)血管的收縮及舒張作用都具有濃度依賴性。MCT所誘導(dǎo)的PAH大鼠肺動(dòng)脈的內(nèi)皮依賴性血管收縮及舒張反應(yīng)、非內(nèi)皮依賴性血管舒張反應(yīng)較CON組均明顯受損,差異有統(tǒng)計(jì)學(xué)意義(P0.05);而IHH干預(yù)后,可顯著改善其受損的內(nèi)皮依賴性的血管收縮及舒張反應(yīng)、非內(nèi)皮依賴性的血管舒張反應(yīng),差異有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:1 SD大鼠經(jīng)腹腔注射野百合堿后14天即能形成明顯的肺動(dòng)脈高壓模型。2間歇性低壓低氧能夠有效降低野百合堿誘導(dǎo)的肺動(dòng)脈高壓大鼠升高的平均肺動(dòng)脈壓及右心室收縮壓。3間歇性低壓低氧能夠有效減輕野百合堿誘導(dǎo)的肺動(dòng)脈高壓大鼠的右心室肥厚。4間歇性低壓低氧對(duì)肺動(dòng)脈高壓大鼠肺血管的內(nèi)皮依賴性血管收縮及舒張反應(yīng)、非內(nèi)皮依賴性血管舒張反應(yīng)均具有重要保護(hù)作用。
[Abstract]:Objective: in recent years, people gradually realize that the plateau hypoxia environment can increase the long-term cardiac resistance to ischemic injury. However, chronic persistent hypoxia and have many adverse effects on the body, such as right ventricular hypertrophy and polycythemia. Many studies show that intermittent hypobaric hypoxia (Intermittent Hypopiesia Hy Poxia, IHH) in the heart has a protective effect of chronic persistent hypoxia, adverse effects on the body is also very low, at the same time, intermittent hypobaric hypoxia is a common form of clinical hypoxia such as coronary heart disease, sleep apnea syndrome. Therefore, IHH has attracted more and more attention. Studies have shown that IHH has many benefits on the body, for example, can protect the nerve and liver and other organs, have a certain role in adjuvant therapy of chronic obstructive bronchitis and bronchial asthma, also reported against ischemia / IHH Reperfusion injury and arrhythmia caused by heart function, enhance the body of ischemia, hypoxia tolerance, but no report has preventive and protective effects on pulmonary hypertension. This experiment used monocrotaline (monocrotaline, MCT) - induced pulmonary arterial hypertension in male SD rats model, observe the effect of IHH on the animal model of lung tissue pulmonary vascular function and morphology, function, and explore the protective mechanism of pulmonary artery, and provide experimental and theoretical basis for the clinical treatment of PAH. The new method provided by the research center of Hebei Medical University animal clean grade healthy male SD 40 rats, the quality of (150-200) g, were randomly divided into 4 groups that is, the normal control group (CON group), pulmonary hypertension group (PAH group), intermittent hypoxia group (IHH group), IHH+MCT group and.CON group rats without any treatment, normal feeding after 28 days of right ventricular systolic pressure (right hear T systolic pressure, RVSP) and the mean pulmonary arterial pressure (mean pulmonary artery pressure, m PAP) were calculated, the right ventricular hypertrophy index (right ventricular hypertrophy index, RVHI) parallel vascular ring perfusion experiment to observe the changes of vascular reactivity in.PAH group by abdominal cavity injection of MCT14 RVSP and m PAP days after the test, the calculation of RVHI and change the.IHH group to observe the vascular reactivity of 5km received simulated altitude hypoxia after 28d intermittent 6h daily detection of RVSP, m PAP, RVHI and.IHH+MCT group to observe the change of the calculation of vascular reactivity to undergo 28d IHH after intraperitoneal injection of MCT, 14 days after the detection of RVSP, m PAP, RVHI and vascular calculation the response of the experiment. All the data were used SPSS 13 statistical software for statistical analysis, the experimental results are subject to the normal distribution of the measurement data, the mean standard deviation of the data between the four groups said. Compared with single factor analysis of variance (One-way ANOVA), a =0.05 level test P0.05, the difference was statistically significant. Results: the death of 1 experimental animal and the general growth of the 1.1 death deaths in group PAH 2 rats, the rats were survived.1.2 growth from the abdominal cavity of rats in the PAH group after MCT injection second week weight compared with the CON group activity, also significantly reduced, tired lying, dyspnea, reduced food intake of rats in the.IHH group activity, group PAH feeding condition and weight were compared to the same period has improved, but compared with the CON group. Right ventricular thickening visible in PAH rats the rats after thoracotomy, pulmonary congestion and swelling, accompanied by ascites, pleural effusion, pericardial effusion and even.2 hemodynamic results of 2.1 rats in each group were m PAP m PAP in the PAH group was significantly higher than that of the other three groups, there were statistically significant differences; the rats in group IHH+MCT than in group PAH m PAP Significantly, the difference was statistically significant (IHH+MCT:19.45 + 1.03 vs PAH:35.28 + 0.94mm Hg, P0.05); the CON group stress level is high, but the difference was not statistically significant (IHH+MCT:19.45 + 1.03 vs CON:16.42 + 0.46mm Hg, P0.05); m PAP and CON group in the IHH group was slightly higher, but there was no statistical significance (IHH:17.86 + 0.42 vs CON:16.42 + 0.46mm Hg, P0.05).2.2 rats RVSP results in the PAH group, RVSP was significantly higher than the other three groups, the differences were statistically significant (PAH:45.14 + 0.62 vs CON:24.46 + 1.21mm Hg, P0.05); group IHH+MCT was significantly lower than that of PAH group, the difference was statistically significant (IHH+MCT:27.58 + 0.98 vs PAH:45.14 + 0.62mm Hg, P0.05 and CON), the group compared to the level of pressure is high, but there was no statistical significance (IHH+MCT:27.58 + 0.98 vs CON:24.46 + 1.21mm Hg, P0.05).IHH group and CON group compared to the high side, but with no statistical significance (IHH:25.74 + 1.16 vs CON:24.46 + 1.2 1mm Hg P0.05.3), right ventricular hypertrophy index (RVHI) calculation of PAH of group RVHI was significantly higher than the other three groups; compared with CON, 2 weeks after monocrotaline injection, rats in PAH group were significantly increased (RVHI PAH:48.76 + 11.7 vs CON:24.43 + 3.79, P0.05) of.IHH+MCT rats was significantly higher than that of RVHI PAH group decreased, the difference was statistically significant (IHH+MCT:25.61 + 4.18 vs PAH:48.76 + 11.7, P0.05); and CON group compared to the level of high pressure, but the pressure has not yet reached the level of CON group, the difference was not statistically significant (IHH+MCT:25.61 + 4.18 vs CON:24.43 + 3.79, P0.05); IHH RVHI group compared with CON group., but there was no statistical significance (IHH:27.66 + 4.17vs CON:24.43 + 3.79, P0.05).4 hypobaric hypoxia on pulmonary artery endothelial function in four experimental groups, Phenylephrine phenylephrine (PHE) from 10-8mol/L to 10-5mol/L can cause vascular endothelium dependent contractile response to acetylcholine. Base Acetylcholine (ACH) from 10-8mol/L to 10-5mol/L can cause vascular endothelium-dependent relaxation, sodium nitroprusside Sodium nitropmsside (SNP) - from 10-8mol/L to 10-5mol/L can induce endothelial vascular endothelial dependent relaxation and contraction and diastolic function above the experimental drug on blood vessels is dependent on the concentration of pulmonary artery induced by.MCT PAH rats dependent vasoconstriction and vasodilation, endothelium dependent vasodilation in CON group were significantly impaired, the difference was statistically significant (P0.05); and the intervention of IHH reaction can significantly improve the impaired endothelium-dependent vascular contraction and relaxation, non endothelium dependent vasodilation. The difference was statistically significant (P0.05). Conclusion: 1 SD rats by intraperitoneal injection of monocrotaline after 14 days can form obvious.2 intermittent pulmonary hypertension model of low pressure and low oxygen can be effectively reduced Right ventricular hypertrophy endothelial.4 intermittent hypobaric hypoxia in rats with pulmonary arterial hypertension induced by monocrotaline low elevated mean pulmonary artery pressure and right ventricular systolic pressure.3 intermittent hypobaric hypoxia can effectively reduce rat pulmonary hypertension induced by monocrotaline on pulmonary vascular of rats with pulmonary hypertension dependent vasoconstriction and vasodilation and non endothelium dependent vasodilation has important protective effects.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R544.1

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