本文選題：高血壓 + H_2S��； 參考：《河北醫(yī)科大學(xué)》2016年博士論文

【摘要】：第一部分硫化氫激活PPARδ/eNOS通路改善高血壓患者腎動(dòng)脈內(nèi)皮依賴(lài)的舒張功能目的:硫化氫(H2S)被證實(shí)為第三種氣體信號(hào)分子,其作為氣體調(diào)質(zhì)在心血管系統(tǒng)發(fā)揮重要作用,具有改善血管內(nèi)皮功能紊亂的作用,但是其保護(hù)內(nèi)皮作用的機(jī)制目前還遠(yuǎn)未闡明清楚。過(guò)氧化物酶體增殖物激活受體δ(peroxisome proliferators-activated receptorδ,PPARδ)作為核受體家族的一員,在代謝方面發(fā)揮的作用已經(jīng)為大家所熟知。最近的研究發(fā)現(xiàn),PPARδ能夠通過(guò)激活eNOS/NO通路增強(qiáng)內(nèi)皮依賴(lài)的舒張功能。因此,我們提出假設(shè)認(rèn)為H2S通過(guò)激活PPARδ/eNOS通路發(fā)揮改善內(nèi)皮的作用。本研究選取高血壓患者和血壓正�；颊叩哪I動(dòng)脈,旨在探討H2S對(duì)PPARδ/eNOS通路的影響,以及是否通過(guò)該通路改善高血壓患者的內(nèi)皮舒張功能紊亂。方法:本實(shí)驗(yàn)選取罹患高血壓或血壓正常并行腎切除患者的腎動(dòng)脈。高血壓患者的入選標(biāo)準(zhǔn)為收縮壓≥140 mmHg或舒張壓≥90 mmHg,不合并糖尿病。入選患者均已簽署知情同意書(shū)。高血壓組和血壓正常組的年齡無(wú)差異(64.00±2.892歲vs 59.92±2.058歲)。高血壓組和正常血壓組的腎動(dòng)脈在加入或不加入硫氫化鈉(NaHS,50μmol/L)的情況下,置于完全DMEM培養(yǎng)基中37℃孵育12 h。孵育后,取腎動(dòng)脈在器官浴槽中檢測(cè)乙酰膽堿(acetylcholine,ACh)誘導(dǎo)的內(nèi)皮依賴(lài)性血管舒張功能。利用Western blot檢測(cè)血管緊張素受體1(AngiotensinⅡreceptor 1,AT1)、胱硫醚-γ-裂解酶(cystathioneγlyase,CSE)、PPARδ、磷酸化內(nèi)皮型一氧化氮和酶(phosphorylated endothelial nitric oxide synthase,p-eNOS)、p-Akt和p-AMPK等相關(guān)蛋白的表達(dá)。人臍靜脈內(nèi)皮細(xì)胞經(jīng)過(guò)AngII處理后,觀察H2S以及各種工具藥對(duì)一氧化氮(nitric oxide,NO)生成量的影響。應(yīng)用激光共聚焦顯微鏡,檢測(cè)NO探針的熒光強(qiáng)度來(lái)反映NO含量。結(jié)果:1高血壓組腎動(dòng)脈對(duì)ach誘導(dǎo)的內(nèi)皮依賴(lài)性的舒張反應(yīng)性較血壓正常組腎動(dòng)脈明顯下降。nahs慢性孵育高血壓患者腎動(dòng)脈可改善內(nèi)皮依賴(lài)性舒張功能。2高血壓組患者的腎動(dòng)脈at1蛋白表達(dá)水平顯著升高,cse蛋白表達(dá)水平下降。nahs慢性孵育可下調(diào)高血壓患者腎動(dòng)脈at1受體表達(dá),增加cse蛋白水平。3高血壓組患者腎動(dòng)脈pparδ蛋白表達(dá)下調(diào),p-enos表達(dá)水平降低。nahs慢性孵育可上調(diào)高血壓患者腎動(dòng)脈pparδ受體表達(dá),提高p-enos表達(dá)水平。4nahs慢性孵育可增加高血壓患者腎動(dòng)脈p-akt和p-ampk蛋白表達(dá)水平。5在培養(yǎng)的人臍靜脈內(nèi)皮細(xì)胞中,nahs可增加血管緊張素ii(angiotensinii,angii)處理的人臍靜脈內(nèi)皮細(xì)胞no生成量。nahs促進(jìn)no生成的作用可被gsk0660(1μmol/l,pparδ受體阻斷劑)、ly294002(5μmol/l,pi3k抑制劑)、wortmanin(0.1μmol/l,pi3k抑制劑)和compoundc(10μmol/l,ampkα抑制劑)部分阻斷。而應(yīng)用at1受體的阻斷劑可發(fā)揮與nahs相似的作用。結(jié)論:h2s可改善高血壓患者內(nèi)皮依賴(lài)性的血管舒張功能,其改善內(nèi)皮功能的作用可能與改善血管內(nèi)源性cse和at1的失衡,以及激活pparδ/enos通路有關(guān)。pi3k/akt和ampk信號(hào)通路可能參與了h2s激活pparδ/enos通路的作用。第二部分硫化氫激活pparδ改善腎血管性高血壓大鼠腎動(dòng)脈內(nèi)皮依賴(lài)的舒張功能目的:大鼠腎血管性高血壓模型是基礎(chǔ)研究中常用的高血壓模型之一。腎血管性高血壓時(shí)腎素-血管緊張素系統(tǒng)(renin-angiotensinsystem,ras)的過(guò)度激活,最終導(dǎo)致內(nèi)皮功能受損。本部分研究利用大鼠腎血管性高血壓模型,進(jìn)一步證實(shí)h2s通過(guò)激活pparδ通路,改善高血壓時(shí)動(dòng)脈內(nèi)皮以來(lái)的舒張功能,并探討其激活pparδ的信號(hào)轉(zhuǎn)導(dǎo)通路。方法:本實(shí)驗(yàn)選用健康雄性spraguedawley(sd)大鼠,7周齡,190-200克,隨機(jī)分為四組:sham組、sham+nahs組、2k1c組和2k1c+nahs組。2k1c和2k1c+nahs組大鼠行兩腎一夾手術(shù)制備腎血管性高血壓模型。sham+nahs和2k1c+nahs組大鼠于兩腎一夾手術(shù)或假手術(shù)后第三周開(kāi)始腹腔注射nahs(56μmol/kg),其余兩組于相同時(shí)間點(diǎn)腹腔注射生理鹽水。每4周通過(guò)鼠尾動(dòng)脈測(cè)量動(dòng)物血壓。第20周末利用小動(dòng)物超聲檢測(cè)腎動(dòng)脈血流量;各組動(dòng)物取腎動(dòng)脈行微血管張力測(cè)定,觀察內(nèi)皮和非內(nèi)皮依賴(lài)性血管舒張功能,并且應(yīng)用pparδ受體阻斷劑gsk0660(1μmol/l)、激動(dòng)劑gw0742(0.1μmol/l)、ampkα磷酸化抑制劑(compoundc10μmol/l)、pi3k的抑制劑ly294002(5μmol/l)和wortmanin(0.1μmol/l)以及no合酶的抑制劑l-name(100μmol/l),通過(guò)慢性孵育2k1c組和2k1c+nahs組大鼠腎動(dòng)脈觀察上述阻斷劑對(duì)nahs作用的影響。利用高壓液相質(zhì)譜法測(cè)定血漿中h2s含量;利用硝酸鹽還原酶法測(cè)定血漿中no含量;he染色觀察腎臟形態(tài)學(xué)變化;利用westernblot檢測(cè)pparδ、cse、p-enos、p-akt和p-ampk等蛋白的表達(dá)水平。結(jié)果:1四組大鼠一般情況監(jiān)測(cè)結(jié)果顯示:2k1c組和2k1c+nahs組大鼠體重在術(shù)后12周開(kāi)始出現(xiàn)增長(zhǎng)緩慢,并一直持續(xù)至實(shí)驗(yàn)結(jié)束。四組動(dòng)物的進(jìn)食量和飲水量無(wú)差異,2k1c組的尿量較其他三組動(dòng)物顯著升高。2慢性外源性給予nahs可顯著降低2k1c大鼠的平均動(dòng)脈壓和血漿中angii水平以及腎動(dòng)脈at1受體蛋白表達(dá)水平。3慢性外源性給予nahs可顯著降低2k1c大鼠左右腎臟重量比、改善腎功能、減輕腎實(shí)質(zhì)形態(tài)學(xué)損傷。4慢性外源性給予nahs可顯著增加2k1c大鼠未鉗夾側(cè)腎血流量。5慢性外源性給予nahs可顯著改善2k1c大鼠內(nèi)皮依賴(lài)性的血管舒張功能,而對(duì)非內(nèi)皮依賴(lài)性的舒張功能無(wú)顯著影響6慢性外源性給予nahs可顯著升高血漿h2s和no含量,上調(diào)腎動(dòng)脈cse蛋白表達(dá)水平。7慢性外源性給予nahs可顯著上調(diào)2k1c大鼠腎動(dòng)脈pparδ和p-enos的蛋白表達(dá)水平。8慢性外源性給予nahs可顯著上調(diào)2k1c大鼠腎動(dòng)脈p-akt和p-ampk的蛋白表達(dá)水平。9應(yīng)用pparδ受體阻斷劑、激動(dòng)劑,ampkα磷酸化抑制劑,pi3k的抑制劑,no合酶的抑制劑,通過(guò)慢性孵育2k1c組和2k1c+nahs組大鼠腎動(dòng)脈,發(fā)現(xiàn)上述阻斷劑可部分或全部阻斷nahs的作用。結(jié)論:h2s可改善高血壓患者內(nèi)皮依賴(lài)性的血管舒張功能,其改善內(nèi)皮功能的作用可能與改善血管內(nèi)源性cse和at1的失衡,以及激活pparδ/enos通路有關(guān)。pi3k/akt和ampk信號(hào)通路可能參與了h2s激活pparδ/enos通路,并進(jìn)而改善高血壓動(dòng)脈內(nèi)皮依賴(lài)性血管舒張功能的作用。第三部分硫化氫通過(guò)下調(diào)bmp4/cox2的表達(dá)改善腎血管性高血壓大鼠腎動(dòng)脈內(nèi)皮依賴(lài)的收縮功能目的:高血壓時(shí),內(nèi)皮功能紊亂一方面表現(xiàn)為內(nèi)皮依賴(lài)的血管舒張功能降低,另一方面表現(xiàn)為內(nèi)皮依賴(lài)的血管收縮功能增強(qiáng)。骨形成蛋白4(bonemorphogenicprotein4,bmp4)屬于轉(zhuǎn)化生長(zhǎng)因子β(transforminggrowthfactor-β,tgf-β)超家族,主要調(diào)節(jié)骨骼的胚胎發(fā)育和再生修復(fù)。最近研究發(fā)現(xiàn),bmp4在心血管系統(tǒng)中發(fā)揮重要作用。bmp4通過(guò)增加nadph氧化酶的表達(dá)和活性,促進(jìn)活性氧自由基(reactiveoxygenspecies,ros)過(guò)度生成,進(jìn)而增加環(huán)氧酶2(cyclooxygenase2,cox2)活性,導(dǎo)致前列腺素類(lèi)物質(zhì)生成和釋放增多,從而損傷血管內(nèi)皮,增強(qiáng)血管內(nèi)皮依賴(lài)的收縮功能,最終促進(jìn)高血壓形成。已有研究顯示,bmp4/cox2表達(dá)增加與自發(fā)性高血壓大鼠內(nèi)皮依賴(lài)性的血管收縮功能增強(qiáng)有關(guān)。本研究利用2k1c制備的高血壓大鼠模型,旨在觀察h2s改善高血壓大鼠內(nèi)皮依賴(lài)的血管收縮功能,并觀察h2s對(duì)bmp4/cox2表達(dá)的影響。方法:健康雄性sd大鼠,7周齡,190-200克,隨機(jī)分為四組:sham組、sham+nahs組、2k1c組和2k1c+nahs組。2k1c和2k1c+nahs組大鼠行兩腎一夾手術(shù)制備腎血管性高血壓模型。sham+nahs和2k1c+nahs組大鼠于兩腎一夾手術(shù)或假手術(shù)后第三周開(kāi)始腹腔注射nahs(56μmol/kg),其余兩組于相同時(shí)間點(diǎn)腹腔注射生理鹽水。開(kāi)始應(yīng)用nahs后每4周通過(guò)鼠尾動(dòng)脈測(cè)量動(dòng)物血壓;第20周末各組動(dòng)物取腎動(dòng)脈行微血管張力的測(cè)定,觀察血管內(nèi)皮依賴(lài)性的收縮功能;利用高壓液相質(zhì)譜法測(cè)定血漿中h2s的含量;利用westernblot檢測(cè)cse、at1、bmp4、cox2以及氧化應(yīng)激相關(guān)蛋白的表達(dá)水平;利用試劑盒檢測(cè)sod活性和mda含量。結(jié)果1 2K1C高血壓大鼠慢性給予NaHS處理,可顯著降低大鼠動(dòng)脈血壓,上調(diào)CSE蛋白表達(dá),增加血漿中H2S含量。2 2K1C大鼠腎動(dòng)脈內(nèi)皮依賴(lài)性收縮功能顯著增強(qiáng)。外源性給予NaHS可改善高血壓大鼠內(nèi)皮依賴(lài)性血管收縮功能。3外源性給予NaHS可顯著下調(diào)腎血管性高血壓大鼠腎動(dòng)脈中AT1受體和BMP 4的蛋白表達(dá)。4外源性給予NaHS可顯著降低腎血管性高血壓大鼠體內(nèi)氧化應(yīng)激水平,氧化應(yīng)激相關(guān)蛋白NOX2、NOX4、P67、Nitrotysine表達(dá)增加。5外源性給予NaHS可顯著升高SOD活性,降低MDA含量。6外源性給予NaHS可顯著改變p38 MAPK和COX-2的蛋白表達(dá)水平。結(jié)論:H2S可顯著改善高血壓大鼠腎動(dòng)脈血管內(nèi)皮依賴(lài)的收縮功能,其改善內(nèi)皮功能的作用可能與抑制BMP4/ROS/COX2通路有關(guān)。
[Abstract]:The first part of hydrogen sulfide activates the PPAR Delta /eNOS pathway to improve the endothelium-dependent diastolic function of renal artery in hypertensive patients: hydrogen sulfide (H2S) is proved to be a third gas signal molecule, which plays an important role in the cardiovascular system as a gas conditioner and has the effect of improving vascular endothelial dysfunction, but it protects the endothelial function. The system is far from clear. As a member of the nuclear receptor family, the peroxisome proliferators-activated receptor delta (PPAR delta), a member of the nuclear receptor family, is known to play a role in metabolism. Recent studies have found that PPAR delta can enhance endothelium dependent relaxation by activating the eNOS/NO pathway. Therefore, we hypothesized that H2S plays the role of improving the endothelium by activating the PPAR Delta /eNOS pathway. In this study, the renal arteries of patients with hypertension and normal blood pressure were selected to explore the effect of H2S on the PPAR Delta /eNOS pathway and to improve the endothelium diastolic dysfunction in hypertensive patients. Methods: this experiment The renal arteries of patients with hypertension or normal blood pressure and normal nephrectomy were selected. The standard of hypertension patients was systolic pressure more than 140 mmHg or diastolic pressure more than 90 mmHg, without diabetes. The patients who were selected had signed informed consent. There was no difference between the hypertension group and the normal blood pressure group (64 + 2.892 years vs 59.92 + 2.058 years old). The renal arteries in the group and the normal blood pressure group were incubated at 37 centigrade for 12 h. under the condition of adding or not adding sodium hydrogen sulfide (NaHS, 50 u mol/L). The endothelium dependent vasodilatation function induced by acetylcholine (acetylcholine, ACh) in the organ bath was detected by the renal artery in the complete DMEM medium. The angiotensin was detected by Western blot. Receptor 1 (Angiotensin II receptor 1, AT1), cystthioether - gamma lyase (cystathione gamma lyase, CSE), PPAR Delta, phosphorylated endothelial nitric oxide and enzyme (phosphorylated endothelial nitric oxide synthase, phosphorylated) and other related proteins. Effect of drug on the production of nitric oxide (nitric oxide, NO). The use of laser confocal microscope to detect the fluorescence intensity of NO probe to reflect the NO content. Results: 1 the renal artery to ach induced endothelium dependent diastolic responsiveness in the hypertensive group was better than that of the normal blood pressure group and the renal artery decreased significantly in the renal artery, and the renal artery could be improved in the.Nahs chronic incubated hypertensive patients. The expression of AT1 protein in renal artery was significantly increased in the patients with endothelium dependent diastolic function in.2 hypertension group, and the decrease of CSE protein expression level in.Nahs chronic incubation could reduce the expression of AT1 receptor in renal artery in hypertensive patients, increase the level of PPAR delta protein in renal artery of.3 hypertension group, and decrease the p-enos expression level to reduce the chronic incubation of.Nahs. Raising the expression of PPAR delta receptor in renal artery in hypertensive patients and increasing p-enos expression level.4nahs chronic incubation can increase the expression level of p-Akt and p-ampk protein in renal artery of hypertensive patients in cultured human umbilical vein endothelial cells. NaHS can increase the no production of umbilical vein endothelial cells treated by angiotensin II (AngiotensinII, AngII). .nahs promotes no formation by gsk0660 (1 mu mol/l, PPAR delta receptor blocker), LY294002 (5 mol/l, PI3K inhibitor), wortmanin (0.1 mu mol/l, PI3K inhibitor) and compoundc (10 micron, alpha inhibitor). The vasodilatation function, which improves endothelial function, may improve the imbalance of endogenous CSE and AT1, and the activation of the.Pi3k/akt and AMPK signaling pathways of the PPAR Delta /enos pathway may be involved in the H2S activation of the PPAR Delta /enos pathway. The second part of hydrogen sulfide activates PPAR delta to improve the renal artery in renovascular hypertensive rats The objective of skin dependent diastolic function: the model of renovascular hypertension in rats is one of the commonly used hypertension models in basic research. The excessive activation of the renin angiotensin system (renin-angiotensinsystem, RAS) in renal vascular hypertension eventually leads to the damage of the endothelial function. One step confirmed that H2S could improve the diastolic function of arterial endothelium in hypertension by activating the PPAR delta pathway and explore the signal transduction pathway to activate PPAR Delta. Methods: this experiment selected healthy male spraguedawley (SD) rats, 7 weeks old and 190-200 grams, randomly divided into four groups: sham group, sham+nahs group, 2K1C group and 2k1c+nahs group.2k1c and 2k1c+nahs group Rats were treated with two kidney one clip operation to prepare renal vascular hypertension model.Sham+nahs and 2k1c+nahs rats. NaHS (56 mol/kg) was injected into the abdominal cavity at third weeks after two kidney one clip operation or sham operation. The rest two groups were injected with normal saline at the same time point. The blood pressure was measured by the rat tail moving pulse every 4 weeks. The twentieth weekend was used by small animals. The renal artery blood flow was measured by sound. The microvascular tension of the renal arteries was measured in each group. The endothelium and non endothelium dependent vasodilatation were observed. The PPAR delta receptor blocker gsk0660 (1 mu mol/l), the agonist GW0742 (0.1 mu mol/l), the AMPK alpha phosphorylation inhibitor (compoundc10 mu mol/l), the PI3K inhibitor LY294002 (5 mu mol/l) and wortmanin were used. (0.1 mu mol/l) and the inhibitor of NO synthase inhibitor L-NAME (100 mol/l), the effects of these blockers on NaHS were observed by chronic incubation of 2K1C group and rat renal artery in group 2k1c+nahs. The content of H2S in plasma was measured by high pressure liquid chromatography-mass spectrometry, and the content of no in plasma was measured by nitrate reductase; he staining was used to observe the morphological changes of kidney; The expression level of PPAR Delta, CSE, p-enos, p-Akt and p-ampk was detected by Westernblot. Results: 1 the general monitoring results of the four groups of rats showed that the weight of the 2K1C group and the 2k1c+nahs group began to grow slowly at 12 weeks after the operation, and continued until the end of the experiment. There was no difference between the intake of the four groups of animals and the amount of drinking water, and the urine volume of the 2K1C group was more than that of the group of 2K1C. The other three groups of animals significantly increased.2 chronic exogenous NaHS can significantly reduce the average arterial pressure and plasma AngII level in 2K1C rats and the expression level of AT1 receptor protein in renal artery,.3 chronic exogenous administration of NaHS can significantly reduce the kidney weight ratio of 2K1C rats, improve renal function and alleviate the chronic renal parenchyma morphological injury.4 chronic exogenous exogenous disease. Sexual administration of NaHS significantly increased the non clamp side renal blood flow of 2K1C rats.5 chronic exogenous NaHS could significantly improve the endothelium-dependent vasodilatation of 2K1C rats, but there was no significant effect on the non endothelium-dependent diastolic function. 6 chronic exogenous administration of NaHS could significantly increase the content of H2S and no in the plasma and up regulation of the expression of CSE protein in the renal artery. Horizontal.7 chronic exogenous administration of NaHS can significantly increase the protein expression level of PPAR Delta and p-enos in renal artery of 2K1C rats,.8 chronic exogenous administration of NaHS can significantly increase the protein expression level of p-Akt and p-ampk in renal artery of 2K1C rats,.9 application of PPAR delta receptor blockers, agonists, inhibitors, inhibitors, inhibition of synthase Agents, through chronic incubation of 2K1C and 2k1c+nahs rats' renal arteries, found that the above blockers could partially or completely block the role of NaHS. Conclusion: H2S can improve the endothelium dependent vasodilatation function of hypertensive patients. Its effect on improving endothelial function may be associated with the improvement of the imbalance of endovascular CSE and AT1, and the activation of the PPAR Delta /enos pathway. The.Pi3k/akt and AMPK signaling pathways may participate in H2S activation of the PPAR Delta /enos pathway and further improve the role of vascular endothelium dependent vasodilatation in hypertensive arteries. The third part of hydrogen sulfide can improve the systolic function of the renal artery endothelium of renal vascular hypertensive rats by downregulating the expression of bmp4/cox2: endothelial function in hypertension On the one hand, the dysfunction of endothelium dependent vasodilatation is reduced, on the other hand, the endothelial dependent vasoconstrictor function is enhanced. Bone morphogenetic protein 4 (bonemorphogenicprotein4, BMP4) belongs to the superfamily of transforming growth factor beta (transforminggrowthfactor- beta, tgf- beta), which mainly regulates the embryonic development and regenerative repair of bone. Recent studies have found that BMP4 plays an important role in the cardiovascular system,.Bmp4 promotes the overproduction of reactive oxygen free radicals (reactiveoxygenspecies, ROS) by increasing the expression and activity of NADPH oxidase, and then increases the activity of epoxy enzyme 2 (cyclooxygenase2, COX2), which leads to the increase of the formation and release of the precursor adenins, thus damaging the vascular endothelium. Enhancing the vasoconstrictor function of vascular endothelium-dependent and ultimately promoting hypertension. Studies have shown that the increase of bmp4/cox2 expression is related to the enhancement of endothelium dependent vasoconstrictor function in spontaneously hypertensive rats. The aim of this study was to observe the endothelium dependent vasoconstriction in hypertensive rats by using the 2K1C model. Function, and observe the effect of H2S on the expression of bmp4/cox2. Methods: healthy male SD rats, 7 weeks old, 190-200 grams, were randomly divided into four groups: sham, sham+nahs, 2K1C and 2k1c+nahs groups.2k1c and 2k1c+nahs rats were treated with two kidney one clip operation to prepare the renal vascular hypertension model.Sham+nahs and 2k1c+nahs group rats in two kidney one clip operation or artificial hand Third weeks after the operation, the intraperitoneal injection of NaHS (56 mol/kg) and the other two groups were intraperitoneally injected with saline at the same time. The blood pressure was measured by the rat tail artery every 4 weeks after the application of NaHS. The renal artery was measured at the end of the twentieth week, and the vasoconstriction of the vascular endothelial dependence was observed, and the high pressure liquid mass spectrometry was used. The content of H2S in plasma was measured and the expression level of CSE, AT1, BMP4, COX2, and oxidative stress related proteins was detected by Westernblot. The activity of SOD and the content of MDA were detected by the kit. Results the arterial blood pressure, the expression of CSE protein and the H2S content in the plasma could be significantly reduced in 1 2K1C hypertensive rats. Endothelium dependent contractile function of renal artery in rats was significantly enhanced. Exogenous administration of NaHS could improve endothelium-dependent vasoconstrictor function of hypertensive rats.3 exogenous NaHS could significantly downregulate the protein expression of AT1 receptor and BMP 4 in renal artery of renovascular hypertensive rats. Exogenous NaHS could significantly reduce renal vascular hypertension. Oxidative stress level, oxidative stress related protein NOX2, NOX4, P67, Nitrotysine expression increased.5 exogenous NaHS can significantly increase SOD activity, decrease MDA content.6 exogenous NaHS can significantly change p38 MAPK and protein expression level. Conclusion: it can significantly improve the renal artery endothelium dependence in hypertensive rats The role of systolic function in improving endothelial function may be related to inhibition of BMP4/ROS/COX2 pathway.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R544.1

【參考文獻(xiàn)】

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1 Hyun Jung Lee;Jong Eun Yeon;Eun Jung Ko;Eileen L Yoon;Sang Jun Suh;Keunhee Kang;Hae Rim Kim;Seoung Hee Kang;Yang Jae Yoo;Jihye Je;Beom Jae Lee;Ji Hoon Kim;Yeon Seok Seo;Hyung Joon Yim;Kwan Soo Byun;;Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease[J];World Journal of Gastroenterology;2015年45期

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本文編號(hào)：1809657