本文選題：整合素連接激酶 + 高血壓�。� 參考：《臨床心血管病雜志》2017年02期

【摘要】：目的:通過(guò)了解整合素連接激酶(ILK)及心肌素(myocardin)在低氧性肺動(dòng)脈高壓(PAH)大鼠肺組織及肺血管中的表達(dá),探討ILK在低氧性肺動(dòng)脈高壓發(fā)病機(jī)制中的作用。方法:48只SD大鼠按隨機(jī)數(shù)字表法分為常氧對(duì)照組和低氧1周、2周、4周組,低氧干預(yù)大鼠置于低氧倉(cāng)內(nèi),氧濃度控制在(10.5±0.5)%,每日間斷低氧8h(8:00~16:00)。測(cè)定各組大鼠肺動(dòng)脈平均壓(mPAP)、計(jì)算右室肥厚指數(shù)[右室/(左室+室間隔),RV/(LV+S)]、管壁厚度占血管外徑的百分比(WT%)和管壁面積占血管總面積的百分比(WA%);采用髓鞘堿性蛋白為底物通過(guò)液體閃爍儀測(cè)定ILK活性;實(shí)時(shí)定量PCR法測(cè)定肺動(dòng)脈內(nèi)ILK、糖原合成激酶3β(GSK-3β)及myocardin mRNA相對(duì)表達(dá)量;Western印跡法檢測(cè)肺動(dòng)脈及培養(yǎng)的肺動(dòng)脈平滑肌細(xì)胞(PASMC)胞質(zhì)內(nèi)ILK、GSK-3β及myocardin蛋白相對(duì)表達(dá)量。結(jié)果:低氧2周組mPAP、右室肥厚指數(shù)、WT%、WA%均顯著高于常氧對(duì)照組(均P0.05),低氧4周組差異更為顯著。低氧1周組肺動(dòng)脈內(nèi)ILK活性即明顯下降達(dá)36%(P0.05),低氧2周、4周組ILK活性均較常氧對(duì)照組明顯降低(均P0.05)。低氧4周組ILK mRNA和蛋白相對(duì)表達(dá)量均顯著低于常氧對(duì)照組(均P0.05),myocardin mRNA和蛋白表達(dá)變化與ILK相似(均P0.05),而GSK-3β的mRNA和蛋白表達(dá)量則呈相反趨勢(shì),顯著高于常氧對(duì)照組(均P0.05)。低氧培養(yǎng)PASMC 24h后ILK及myocardin蛋白表達(dá)明顯低于常氧對(duì)照組,而GSK-3β蛋白水平則呈相反趨勢(shì),低氧可促進(jìn)其表達(dá)增加(均P0.05)。結(jié)論:慢性低氧引起ILK活性和表達(dá)下調(diào),使其下游靶點(diǎn)GSK-3β表達(dá)上調(diào),進(jìn)而降低myocardin表達(dá)水平,可能是導(dǎo)致PAH形成的重要機(jī)制。
[Abstract]:Aim: to investigate the expression of integrin linked kinase (ILK) and cardiomyocardinin in lung tissues and pulmonary vessels of rats with hypoxic pulmonary hypertension (hypoxic pulmonary hypertension) and to explore the role of ILK in the pathogenesis of hypoxic pulmonary hypertension.Methods Forty-eight Sprague-Dawley rats were randomly divided into normoxic control group and hypoxic control group. Hypoxic intervention rats were placed in a hypoxic chamber with oxygen concentration controlled at 10.5 鹵0.5. The rats were exposed to hypoxia for 8 hours a day.The mean pressure of pulmonary artery in each group was measured, and the right ventricular hypertrophy index (RV / LV S), the wall thickness as a percentage of the external diameter of the vessel and the area of the wall as a percentage of the total area of the vessel were calculated, and the myelin basic egg was used to calculate the right ventricular hypertrophy index (RV / LV S), the wall thickness as a percentage of the external diameter of the vessel and the area of the vessel wall as a percentage of the total area of the vessel.The activity of ILK was determined by liquid scintillation instrument.The relative expression of ILK, glycogen synthesis kinase 3 尾 -GSK-3 尾 and myocardin mRNA in pulmonary artery and in cultured pulmonary artery smooth muscle cells (PASMC) was measured by real-time quantitative PCR. The relative expression of ILK- GSK-3 尾 and myocardin protein in the cytoplasm of pulmonary artery and cultured pulmonary artery smooth muscle cells was detected by Western blot.Results: the mPAPand WA% of right ventricular hypertrophy in hypoxia 2 weeks group were significantly higher than those in normoxic control group (P 0.05), and the difference was more significant in hypoxia 4 weeks group.The activity of ILK in pulmonary artery of hypoxic group decreased significantly to 36% P0.05, and the activity of ILK in hypoxic group for 2 weeks and 4 weeks was significantly lower than that in normal control group (P0.05%, all P0. 05%, P 0. 05%, P 0. 05%, P 0. 05%).The relative expression of ILK mRNA and protein in hypoxia group was significantly lower than that in normoxic control group (P 0.05). The expression of myocardin mRNA and protein was similar to that of ILK (P 0.05), but the expression of mRNA and protein of GSK-3 尾 was significantly higher than that of normoxic control group (P 0.05).The expression of ILK and myocardin protein was significantly lower than that of normoxic control group after 24 hours of hypoxia culture, while the level of GSK-3 尾 protein showed a reverse trend. Hypoxia could promote the expression of ILK and myocardin protein (all P 0.05).Conclusion: chronic hypoxia induces down-regulation of ILK activity and expression, up-regulates the expression of GSK-3 尾 and reduces the level of myocardin expression, which may be an important mechanism leading to the formation of PAH.
【作者單位】： 東南大學(xué)附屬中大醫(yī)院心內(nèi)科;
【分類號(hào)】：R544.1

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