本文選題：酸中毒 + 冠狀動脈��； 參考：《山西醫(yī)科大學》2017年碩士論文

【摘要】：目的:觀察酸中毒(pH_(ex)6.8)對大鼠離體冠狀動脈(coronary artery,CA)靜息張力的影響,并探討其作用機制。通過觀察Na+-H+交換體亞型1(NHE-1)抑制劑和Na+-HCO3-共同轉(zhuǎn)運體(NBC)抑制劑對pH_(ex)6.8收縮大鼠離體CA的影響,探討酸堿轉(zhuǎn)運體在酸中毒引起大鼠離體CA收縮中的作用;通過觀察氯通道阻滯劑(NPPB和NFA)及細胞外去除氯離子對pH_(ex)6.8收縮大鼠離體CA的影響,探討氯離子跨細胞膜轉(zhuǎn)運在酸中毒引起大鼠離體CA收縮中的作用;通過觀察Rho激酶(ROCK)抑制劑、蛋白激酶C(PKC)抑制劑和細胞外調(diào)節(jié)蛋白激酶(ERK)抑制劑對pH_(ex)6.8收縮大鼠離體CA的影響,探討蛋白激酶在酸中毒引起大鼠離體CA收縮中的作用。方法:1.將SD雄性青年大鼠(230~260 g)斷頭處死后,快速從胸腔內(nèi)取出心臟,置于4℃、pH 7.40、95%O_2+5%CO_2飽和的生理鹽溶液(Physiological saline solution,PSS)中。在解剖顯微鏡下,用顯微剪和顯微鑷將大鼠冠狀動脈(室壁支、室間隔支及前降支)快速分離干凈,游離出來,剪成約2 mm長的冠脈血管環(huán),固定于微血管張力記錄儀(Multi Myograph System-610M,DMT)。采用Power Lab微血管環(huán)張力系統(tǒng),記錄大鼠離體CA血管環(huán)的張力。2.分別觀察NHE-1選擇性抑制劑HOE-642(30μmol/L)預孵和NBC抑制劑S0859(100μmol/L)預孵對pH_(ex)6.8引起大鼠離體CA收縮的影響。3.分別觀察氯離子通道阻滯劑NPPB(10、30、100μmol/L)和NFA(10、30、100μmol/L)對pH_(ex)6.8引起大鼠離體CA收縮的影響;分別觀察氯離子通道阻滯劑NPPB(10、30、100、300μmol/L)和NFA(10、30、100、300μmol/L)對KCl(60 mmol/L)引起大鼠離體CA收縮的影響;以及分別觀察NPPB(100μmol/L)和NFA(100μmol/L)對血栓素A2類似物U46619(1μmol/L)引起大鼠離體CA收縮的影響。此外,觀察用L-天冬氨酸鈉等量代替細胞外PSS液中氯化鈉后,對pH_(ex)6.8、KCl(60 mmol/L)和U46619(1μmol/L)引起大鼠離體CA收縮的影響。4.分別觀察ROCK抑制劑Y-27632(3μmol/L)、PKC抑制劑G?6983(1μmol/L)和ERK抑制劑PD98059(10μmol/L)對pH_(ex)6.8引起大鼠離體CA收縮的影響。結(jié)果:1.在靜息狀態(tài)時,pH_(ex)6.8引起大鼠離體CA張力升高,最大張力為(3.90±0.95)m N,相當于KCl(60 mmol/L)最大收縮幅度的(105.07±10.65)%。2.HOE-642(30μmol/L)使pH_(ex)6.8引起的大鼠離體CA收縮幅度降低(18.46±5.29)%(P0.01),S0859(100μmol/L)使其收縮幅度降低(14.90±3.24)%(P0.01)。3.NPPB和NFA均濃度依賴性(10、30、100μmol/L)地抑制pH_(ex)6.8引起的大鼠離體CA收縮,最大抑制百分比分別為(66.61±7.07)%(P0.01)和(64.48±11.68)%(P0.01)。NPPB和NFA均濃度依賴性(10、30、100、300μmol/L)地抑制KCl(60 mmol/L)引起的大鼠離體CA收縮,最大抑制百分比分別為(83.51±3.13)%(P0.01)和(52.37±12.31)%(P0.01)。NPPB(100μmol/L)和NFA(100μmol/L)均可抑制U46619(1μmol/L)引起的大鼠離體CA收縮,其抑制百分比分別為(44.04±9.68)%(P0.01)和(46.23±5.24)%(P0.01)。用L-天冬氨酸鈉代替PSS溶液中的Na Cl后,幾乎完全抑制pH_(ex)6.8引起的大鼠離體CA收縮(P0.01),而對KCl(60 mmol/L)和U46619(1μmol/L)引起的大鼠離體CA收縮無顯著影響(P0.05)。4.Y-27632(3μmol/L)、G?6983(1μmol/L)和PD98059(10μmol/L)均可抑制pH_(ex)6.8引起的大鼠離體CA收縮,其抑制百分比分別為(29.37±13.44)%(P0.01)、(29.84±10.58)%(P0.01)和(23.14±9.47)%(P0.01)。結(jié)論:1.酸中毒引起大鼠離體CA收縮與激活NHE-1和NBC有關。2.氯離子跨細胞膜轉(zhuǎn)運和氯離子通道在酸中毒引起大鼠離體CA收縮中起重要作用。3.酸中毒引起大鼠離體CA收縮與激活ROCK、PKC和ERK有關。
[Abstract]:Objective: To observe the effect of acidosis (pH_ (Ex) 6.8) on resting tension of isolated coronary artery (coronary artery (CA)) in rats and explore its mechanism of action. The effect of Na+-H+ exchange body subtype 1 (NHE-1) inhibitor and Na+-HCO3- common transporter (NBC) inhibitor on pH_ (Ex) 6.8 rats' isolated CA was investigated, and the acid base transporter in acidosis was investigated. By observing the effect of chlorine channel blockers (NPPB and NFA) and the effect of chlorine ion removal from pH_ (Ex) 6.8 in vitro CA in vitro, the effect of chloride ion transcellular membrane transport on the contraction of CA in rats in vitro was investigated. By observing the inhibitors of Rho kinase (ROCK), protein kinase C (PKC) inhibitors and CA The effect of extracellular regulated protein kinase (ERK) inhibitor on the isolated CA in pH_ (Ex) 6.8 rat in vitro, and to explore the role of protein kinase in the contraction of CA in rats induced by acidosis. Method: 1. after the death of SD male young rats (230~260 g), the heart was quickly removed from the thoracic cavity and placed at 4, pH 7.40,95%O_2+5%CO_2 saturated physiological salt solution. (Physiological saline solution, PSS). Under the anatomical microscope, the coronary artery (ventricular wall, interventricular septum branch and anterior descending branch) of rats were quickly separated and cleaned by microscissors and microtweezers, free and cut into about 2 mm long coronary vessels, fixed to the microvascular tension recorder (Multi Myograph System-610M, DMT). Power Lab microvessels were used. Cyclic tension system, the tension.2. of CA vascular rings in rats was recorded. The effect of NHE-1 selective inhibitor HOE-642 (30 mu mol/L) pre incubation and NBC inhibitor S0859 (100 micron mol/L) preincubation on pH_ (Ex) 6.8 induced CA contraction in rats was observed, and.3. channel blockers were observed and 6. were observed respectively. 8 the effect of CA contraction in rats in vitro; the effect of chloride channel blocker NPPB (10,30100300 mu mol/L) and NFA (10,30100300 mu mol/L) on KCl (60 mmol/L) induced contraction of rat CA in vitro; and the contraction of thromboxane analogues (1 mu), respectively, caused by NPPB (100 micron) and 100 micron (1 mu) In addition, the effect of sodium chloride on pH_ (Ex) 6.8, KCl (60 mmol/L) and U46619 (1 mu mol/L) induced CA contraction in rats was observed with sodium aspartic acid (L- aspartate). The.4. ROCK inhibitor Y-27632 (3 MU), 6983 (1 mu) and 10 micron (10 mu) for 6.8 were observed. The effect of CA contraction in rat in vitro. Results: 1. in resting state, pH_ (Ex) 6.8 causes the increase of CA tension in rats in vitro, the maximum tension is (3.90 + 0.95) m N, which is equivalent to (105.07 + 10.65)%.2.HOE-642 (30 micron mol/L) of the maximum contraction amplitude of KCl (60 mmol/L), which reduces the contraction amplitude of rats in pH_ (Ex) 6.8 (18.46 + 5.29)% (100 mu). L/L) reduced the contraction amplitude of (14.90 + 3.24)% (P0.01)% (P0.01).3.NPPB and NFA to inhibit pH_ (Ex) 6.8 induced CA contraction in rats in vitro, and the maximum inhibition percentage was (66.61 + 7.07)% (P0.01) and (64.48 + 11.68)% (P0.01). The maximum inhibitory percentage of rat CA in vitro was (83.51 + 3.13)% (P0.01) and (52.37 + 12.31)% (P0.01).NPPB (100 mu mol/L) and NFA (100 mol/L) could inhibit the contraction of rat CA induced by U46619 (1 micron), and the inhibition percentage was (44.04 + 9.68)% (P0.01) and (46.23 + 5.24)% (P0.01), respectively. After Na Cl in SS solution, it almost completely inhibited the CA contraction (P0.01) of rats in vitro caused by pH_ (Ex) 6.8, but there was no significant effect on KCl (60 mmol/L) and U46619 (1 mu mol/L) of rat isolated CA contraction (3 micron). 6983 (1 mu) and 10 micron (10 mu) could inhibit the contraction of rats in vitro. The percentages were (29.37 + 13.44)% (P0.01), (29.84 + 10.58)% (P0.01) and (23.14 + 9.47)% (P0.01). Conclusion: 1. acid poisoning caused CA contraction in rats in vitro and activation of NHE-1 and NBC related to the trans cell membrane transport of.2. chloride ions and the effect of chlorine ion channel on the contraction of CA in rat isolated CA caused by.3. acidosis. Contraction is related to activation of ROCK, PKC and ERK.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R54

【參考文獻】

相關期刊論文 前3條

1 陳偉偉;高潤霖;劉力生;朱曼璐;王文;王擁軍;吳兆蘇;李惠君;鄭哲;蔣立新;胡盛壽;;《中國心血管病報告2014》概要[J];中國循環(huán)雜志;2015年07期

2 李江濤;劉宇;牛龍剛;崔麗娟;侯曉敏;李金艷;郭永強;張明升;;細胞外酸性環(huán)境對大鼠冠狀動脈環(huán)靜息張力的影響及其與鉀通道阻斷劑的關系[J];中西醫(yī)結(jié)合心腦血管病雜志;2014年09期

3 黃林靜;王淑君;何金波;馬迎春;應磊;陳錫文;王萬鐵;;氯離子通道阻滯劑通過抑制MAPK通路減輕低氧高二氧化碳性肺血管收縮[J];溫州醫(yī)科大學學報;2014年01期

相關博士學位論文 前2條

1 牛龍剛;酸中毒對大鼠冠脈平滑肌張力的影響及機制研究[D];山西醫(yī)科大學;2014年

2 胡弋;缺血預處理和藥物預處理對失血性休克大鼠血管反應性和鈣敏感性的影響及其與Rho激酶的關系[D];第三軍醫(yī)大學;2011年

，

本文編號：2068249