發(fā)布時間：2018-01-17 23:09

  本文關(guān)鍵詞：甘氨酸拮抗內(nèi)毒素性心臟損傷的作用及機制研究　出處：《暨南大學(xué)》2007年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 甘氨酸 內(nèi)毒素 心臟損傷 血流動力學(xué) 腫瘤壞死因子α 凋亡蛋白酶3 凋亡

【摘要】： 目的 內(nèi)毒素血癥的死亡率仍具高不下，且內(nèi)毒素血癥患者一旦并發(fā)心功能損傷，其死亡率將大大提高，但是目前臨床上尚未找到行之有效的藥物。本室多年的研究證實甘氨酸(Gly)能有效拮抗內(nèi)毒素(LPS)，并有心肌細胞保護作用。本研究擬在上述研究的基礎(chǔ)上，在體研究預(yù)防性給予Gly能否拮抗LPS誘導(dǎo)的大鼠心臟損傷，并進一步探討其保護機制，，為臨床內(nèi)毒素血癥的防治提供理論依據(jù)。 方法 研究分為2個部分進行。 1．Gly對LPS導(dǎo)致的大鼠心臟損傷的影響。實驗動物被隨機分為5組，分別是NS組、LPS組、20％Gly+LPS組、10％Gly+LPS組、5％Gly+LPS，給予LPS或生理鹽水4h后，各組取部分動物進行左心室插管，測定各組動物血流動力學(xué)的變化；全自動生化分析儀測定剩余動物血清中心肌酶(LDH、CK)活性的變化，并通過透射電鏡觀察動物心肌超微結(jié)構(gòu)的變化，從三個方面判斷LPS性心臟損傷模型制備是否成功，并觀察Gly對LPS誘導(dǎo)的心臟損傷的影響。 2．探討Gly拮抗LPS性心臟損傷的機制。運用ELISA法檢測血清中和心肌組織中TNFα的含量；化學(xué)比色法檢測心肌組織中caspase-3活力；TUNEL法測定各組動物的心肌細胞調(diào)亡率，從循環(huán)中和心肌細胞局部TNFα的表達量和心肌細胞凋亡方面探討Gly拮抗LPS性心臟損傷的機制。 結(jié)果 1．血流動力學(xué)分析結(jié)果顯示：LPS組反映心臟收縮功能的左心室收縮壓(LVSP)和左心室內(nèi)壓最大上升速率(+dp／dtmax)降低，反映心臟舒張功能的左心室終末舒張壓(LVEDP)和左心室內(nèi)壓最大下降速率(-dp／dtmax)升高，與NS組比較差異有顯著性(P＜0.01)，Gly防治組上述指標(biāo)優(yōu)于LPS組，其中10％Gly+LPS組LVEDP、+dp／dtmax與LPS組比較差異有顯著性(P＜0.05)；LPS組LDH、CK活力升高，與NS組比較差異有顯著性(P＜0.05)，所有Gly防治組LDH活力與LPS組比明顯降低(P＜0.05)；透射電鏡下觀察，LPS組心肌纖維斷裂溶解，心肌細胞核染色質(zhì)邊集、細胞核皺縮、核碎裂，線粒體腫脹、部分線粒體空泡化，Gly防治組心肌細胞超微結(jié)構(gòu)損傷有明顯改善。 2．LPS組血清和心肌組織中TNFα表達量較NS組明顯升高(P＜0.01)，10％Gly+LPS組和5％Gly+LPS組血清中的TNFα含量低于LPS組(P＜0.01)，10％Gly+LPS組和5％Gly+LPS組中心肌細胞中的TNFα含量亦低于LPS組(P＜0.05)；LPS組心肌細胞的caspase-3活力較NS組明顯升高(P＜0.01)，10％Gly+LPS和5％Gly+LPS組心肌細胞的caspase-3活力降低，與LPS組比較差異有顯著性(P＜0.05)；TUNEL法顯示LPS組有大量心肌細胞凋亡，Gly防治組心肌細胞的調(diào)亡率降低，其中10％Gly+LPS組和20％Gly+LPS組心肌細胞的調(diào)亡率與LPS組比較有顯著性差異(P＜0.01)，5％Gly+LPS組心肌細胞的調(diào)亡率與LPS組比較差異有顯著性(P＜0.05)。 結(jié)論 1．Gly可改善血流動力學(xué)指標(biāo)，減輕在體狀態(tài)下LPS所致的大鼠心功能障礙。 2．Gly能抑制LPS誘發(fā)的心肌酶(LDH)釋放。 3．Gly可抑制LPS所致的心肌細胞超微結(jié)構(gòu)損傷，發(fā)揮心臟保護作用。 4．Gly拮抗LPS性心臟損傷的機制可能與抑制髓樣細胞和心肌細胞分泌TNFα、抑制心肌細胞中caspase-3活化、減少心肌細胞凋亡的發(fā)生有關(guān)。
[Abstract]:objective
The mortality rate of endotoxemia is still high, and once the heart function of patients with endotoxemia complicated with injury, the mortality rate will be greatly improved, but the current clinical drug research has not been found effective. The room for the glycine (Gly) can effectively antagonize endotoxin (LPS), and the protective effect of myocardial cells in this study. On the basis of the above study, the prophylactic administration of Gly can antagonize LPS induced cardiac injury in rats in vivo, and to further explore the protective mechanism, to provide theoretical basis for clinical prevention and treatment of endotoxemia.
Method
The study is divided into 2 parts.
1.Gly on LPS induced rat cardiac injury. The effects of the experimental animal were randomly divided into 5 groups, namely NS group, LPS group, 20%Gly+LPS group, 10%Gly+LPS group, 5%Gly+LPS, LPS or saline 4h, each group to take part in animal left ventricular intubation, changes of hemodynamics were measured animal; Determination of residual animal serum myocardial enzyme automatic biochemical analyzer (LDH, CK) activity changes, and changes of animal myocardial ultrastructure was observed by transmission electron microscope, from three aspects to judge LPS heart injury model preparation is successful, and the effect of Gly on cardiac injury induced by LPS.
2. to investigate the mechanism of Gly against LPS injury of heart. The content of TNF alpha ELISA for detecting serum and myocardial tissues; the activity of Caspase-3 in myocardial tissue were detected by chemical colorimetry; myocardial cell was measured by TUNEL animal death rate, to explore the mechanism of Gly against LPS injury of heart from the expression and apoptosis of myocardial cells the circulation and myocardial cells in local TNF alpha.
Result
1. hemodynamic analysis showed that left ventricular systolic function in LPS group reflected pressure (LVSP) and left ventricular pressure maximal rate of rise (+dp / dtmax) decreased, reflecting the left ventricular diastolic function end diastolic pressure (LVEDP) and left ventricular pressure maximal rate of decrease (-dp / dtmax)., there was significant difference compared with NS group (P < 0.01), Gly control group the index is better than that of LPS group, 10%Gly+LPS group LVEDP, there were significant differences in +dp / dtmax and LPS group (P < 0.05); group LPS, LDH, CK activity increased, compared with the NS group had significantly difference (P < 0.05), all Gly control group and LPS group than the LDH activity decreased significantly (P < 0.05); transmission electron microscope, LPS group myocardial fibers dissolved, myocardial nuclear chromatin, cell shrinkage, nuclear fragmentation, mitochondrial swelling, mitochondrial vacuolization, Gly prevention and treatment of myocardial ultrastructure. The damage of structure is obviously improved.
The amount of TNF alpha were significantly higher than the NS group the expression of 2.LPS in serum and myocardium (P < 0.01), TNF 10%Gly+LPS group and 5%Gly+LPS group alpha content in serum was lower than that of LPS group (P < 0.01), TNF were 10%Gly+LPS group and 5%Gly+LPS group of myocardial cells in the lower than that of group LPS (P < 0.05) LPS; group of myocardial cell caspase-3 activity was higher than that of group NS (P < 0.01), 10%Gly+LPS and 5%Gly+LPS group of myocardial cell caspase-3 activity decreased, there was significant difference compared with LPS group (P < 0.05); TUNEL showed that LPS group had a large number of myocardial cell apoptosis, Gly control group myocardial cell apoptosis rate decreased in the 10%Gly+LPS group and the 20%Gly+LPS group of myocardial cell apoptosis rate and LPS groups had significant difference (P < 0.01), there was significant difference between 5%Gly+LPS group myocardial cell apoptosis rate and LPS group (P < 0.05).
conclusion
1.Gly can improve the hemodynamic index and reduce the cardiac dysfunction in rats induced by LPS in body state.
2.Gly can inhibit the release of myocardial enzymes (LDH) induced by LPS.
3.Gly can inhibit the ultrastructural damage of myocardial cells induced by LPS and play a protective role in the heart.
The mechanism of 4.Gly antagonizing LPS induced cardiac injury may be related to inhibiting the secretion of TNF alpha by medullary cells and cardiomyocytes, inhibiting the activation of Caspase-3 in cardiomyocytes, and decreasing the apoptosis of cardiomyocytes.

【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2007
【分類號】：R363

【參考文獻】

相關(guān)期刊論文 前10條

1 谷俊朝,馬濤,王宇;甘氨酸保護作用機制與相關(guān)疾病探討[J];北京醫(yī)學(xué);2005年09期

2 楊一新;李桂源;;LPS所介導(dǎo)的信號轉(zhuǎn)導(dǎo)通路研究進展[J];中南大學(xué)學(xué)報(醫(yī)學(xué)版);2006年01期

3 錢皓瑜,劉超;甘氨酸減輕油酸誘導(dǎo)的大鼠肺損傷[J];河南職工醫(yī)學(xué)院學(xué)報;2004年02期

4 廉洪;陳歡;杜景霞;胡燕;金滿文;;甘氨酸對離體缺血再灌注大鼠心臟的保護作用[J];華中科技大學(xué)學(xué)報(醫(yī)學(xué)版);2006年06期

5 彭濤,馬曉燕,王英華,周旭;苦豆子總堿對大鼠血流動力學(xué)的影響[J];寧夏醫(yī)學(xué)院學(xué)報;2005年03期

6 戚仁斌,陸大祥,王華東,周華,王海華,李楚杰;甘氨酸拮抗內(nèi)毒素性離體心臟損傷的作用研究[J];中國藥理學(xué)通報;2005年06期

7 賈月霞;潘春水;耿彬;楊靖輝;趙晶;于芳;Helen Gerns;唐朝樞;齊永芬;;Intermedin~(1-53)保護異丙基腎上腺素誘導(dǎo)的心肌損傷[J];中國藥理學(xué)通報;2005年12期

8 戚仁斌,李曉娟,王華東,王海華,陸大祥;甘氨酸抗心肌損傷作用及機制研究[J];中國病理生理雜志;2003年11期

9 張齊好,陸大祥,王華東,戚仁斌,付詠梅,陳莉萍,李楚杰;甘氨酸對心肌缺血-再灌注小鼠一氧化氮系統(tǒng)和Bcl-2mRNA表達的影響[J];中國病理生理雜志;2004年01期

10 李曉娟,陸大祥,王華東,戚仁斌,王彥平,李楚杰;甘氨酸對缺氧/復(fù)氧心肌細胞[Ca~(2+)]i和TNF-α濃度的影響[J];中國病理生理雜志;2004年04期

相關(guān)碩士學(xué)位論文 前1條

1 周瓊;甘氨酸對心肌缺血性損傷的防治作用及機制研究[D];暨南大學(xué);2002年

本文編號：1438367