辣椒素预防大鼠胃缺血再灌注损伤的作用及机制研究
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摘要
本研究为探讨辣椒素(CAP)对大鼠胃缺血再灌注损伤(GI-R)的作用及机制。成年雄性健康SD大鼠40只,随机分为4组,每组10只,A组(空白对照组),B组(手术组),C组(CAP组),D组(CAP+手术组)。给予A组、B组大鼠灌胃生理盐水10 m L/kg/d,C组、D组大鼠灌胃CAP1 mg/kg/d。4周后B组、D组于GI-R模型建立后24小时处死大鼠,收集胃液测定胃酸总酸度,肉眼计数胃黏膜损伤指数,行胃窦组织病理学观察,检测胃黏膜辣椒素受体(TRPV1)、降钙素基因相关肽(CGRP)的表达,检测胃窦组织丙二醛(MDA)、超氧化物歧化酶(SOD)的水平。结果显示A组、C组胃黏膜未见损伤;与B组相比,D组胃黏膜损伤程度显著减轻(P<0.05),胃酸总酸度显著降低(P<0.05),MDA值显著降低(P<0.05),SOD值显著升高(P<0.05),TRPV1、CGRP表达显著增多(P<0.05)。实验结果表明预先给予CAP 1 mg/kg/d连续灌胃4周具有预防缺血再灌注致大鼠胃黏膜损伤的作用,其机制可能与CAP上调TRPV1、CGRP在胃内的表达、减轻氧自由基损伤有关。
This study was to explore the effect and mechanism of capsaicin on gastric ischemia-reperfusion injury in rats.Specific methods were as follows: 40 SD rats were randomly divided into 4 groups with 10 rats in each group,group A( control group),group B( operation group),group C( CAP group) and group D( CAP + operation group). Rats in group A and group B were treated with intragastric administration of normal saline 10 ml/kg/d,group C and group D with intragastric administration of CAP1 mg/kg/d. After 4 weeks,the rats in group B and group D were killed 24 hours later after the establishment of GI-R model. Last,astric juice was collected to determine the total acidity of gastric acid,counted the gastric mucosal injury index,observed the gastric mucosa pathological injury,and detected the expression of TRPV1、CGRP、MDA、SOD.Results show that: the gastric mucosa of group A and C had no damage. Compared with group B,the gastric mucosa injury were significantly reduced( P < 0. 05),total acidity decreased significantly( P < 0. 05),MDA decreased significantly( P < 0. 05),SOD increased significantly( P < 0. 05) and the expression of TRPV1、CGRP increased significantly( P < 0. 05) in group D. Experimental results show that: it could prevent that GI-R induced acute gastric mucosal injury in rats by pretreated with CAP 1 mg/kg/d for 4 weeks. The mechanism may be related to the up regulation of TRPV1 and CGRP expression in the stomach and the reduction of oxygen free radical damage by CAP.
This study was to explore the effect and mechanism of capsaicin on gastric ischemia-reperfusion injury in rats.Specific methods were as follows: 40 SD rats were randomly divided into 4 groups with 10 rats in each group,group A( control group),group B( operation group),group C( CAP group) and group D( CAP + operation group). Rats in group A and group B were treated with intragastric administration of normal saline 10 ml/kg/d,group C and group D with intragastric administration of CAP1 mg/kg/d. After 4 weeks,the rats in group B and group D were killed 24 hours later after the establishment of GI-R model. Last,astric juice was collected to determine the total acidity of gastric acid,counted the gastric mucosal injury index,observed the gastric mucosa pathological injury,and detected the expression of TRPV1、CGRP、MDA、SOD.Results show that: the gastric mucosa of group A and C had no damage. Compared with group B,the gastric mucosa injury were significantly reduced( P < 0. 05),total acidity decreased significantly( P < 0. 05),MDA decreased significantly( P < 0. 05),SOD increased significantly( P < 0. 05) and the expression of TRPV1、CGRP increased significantly( P < 0. 05) in group D. Experimental results show that: it could prevent that GI-R induced acute gastric mucosal injury in rats by pretreated with CAP 1 mg/kg/d for 4 weeks. The mechanism may be related to the up regulation of TRPV1 and CGRP expression in the stomach and the reduction of oxygen free radical damage by CAP.
引文
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3 Guth PH,Paulsen G,Nagata H.Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat:effect of prostaglandin cytoprotection[J].Gastroenterology,1984,87:1083-1090.
4 Masuda E,Kawano S,Nagano K,et al.Role of endogenous endothelin in pathogenesis of ethanol-induced gastric mucosal injury in rats[J].Am J Physiol,1993,265:G474-478.
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6 Su YS,Xin JJ,Yang ZK,et al.Effects of different local moxibustion-like stimuli at zusanli(ST36)and zhongwan(CV12)on gastric motility and its underlying receptor mechanism[J].Evid Based Complement Alternat Med,2015,20:1-8.
7 Hofmann NA,Barth S,Waldeck-Weiermair M,et al.TRPV1mediates cellular uptake of anandamide and thus promotes endothelial cell proliferation and network-formation[J].Biol Open,2014,3:1164-1172.
8 Evangelista S.Capsaicin receptor as target of calcitonin generelated peptide in the gut[J].Prog Drug Res,2014,68:259-76.
9 Magierowski M,Jasons K,Sliwowski Z,et al.Exogenous asymmetric dimethylargigine(ADMA)in pathogenesis of ischemia-reperfusion-induced gastric lesions:interaction with protective nitric oxide(NO)and calcitionin gene-related peptide(CGRP)[J].Int J Mol Sci,2014,15:4946-4964.
10 Tanigawa T,Ahluwalia A,Watanabe T,et al.Nerve growth factor injected into the gastric ulcer base incorporates into endothelial,neuronal,glial and epithelial cells:implications for angiogenesis,mucosal regeneration and ulcer healing[J].J Physiol Pharmacol,2015,66:617-621.
11 Okumi H,Tashima K,Matsumoto K,et al.Dietary agonists of TRPV1 inhibit gastric acid secretion in mice[J].Planta Medica,2012,78:1801-1806.
12 Mózsik.Capsaicin as new orally applicable gastroprotective and therapeutic drug alone or in combination with nonsteroidal anti Inflammatory drugs inhealthy human subjects and in patients[J].Prog Drug Res,2014,68:209-258.
13 Myren J.Gastric secretion following stimulation with histamine,histology and gastrin in man[J].Universitetforlaget Oslo,1968,90:413-428.
14 Ji P(基鹏),Jiang T(姜涛),Li Y(李羽),et al.Influence of capsaicin sensitive c fibers denervation on lung ischemiareperfusion injury[J].J Sichuan Univ:Med Sci(四川大学学报,医学版),2014,45:245-248.
15 Wang M,Jip,W,et al.TRPV1 agonist capsaicin attenuates lung ischemia reperfusion injury in rabbits[J].J Surg Res,2012,173:153-160.
16 Kogure K,Goto S,Nishimura M,et al.Mechanism of potent antiperoxidative effect of capsaicin[J].Biochim Biophys Acta,2002,1573(1):84-92.
17 Tsurugizawa T,Nogusa Y,Ando Y,et al.Different TRPV1-mediated brain responses to intragastric infusion of capsaicin and capsiate[J].Eur J Neurosci,2013,38:3628-3635.
2 Yang F(阳凤),Wang Y(王瑶),Peng Y(彭燕),et al.The effect and mechanism of capsaicin prevented acute gastric mucosal injury by ondomethacin[J].J Practical Med(实用医学杂志),2017,33:1231-1234.
3 Guth PH,Paulsen G,Nagata H.Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat:effect of prostaglandin cytoprotection[J].Gastroenterology,1984,87:1083-1090.
4 Masuda E,Kawano S,Nagano K,et al.Role of endogenous endothelin in pathogenesis of ethanol-induced gastric mucosal injury in rats[J].Am J Physiol,1993,265:G474-478.
5 Shi XM(史孝敏),Li ZP(李泽培),Peng Y(彭燕).Advances in study on TRPV1 in gastrointestinal diseases[J].Gastroenterology(胃肠病学),2013,18:444-446.
6 Su YS,Xin JJ,Yang ZK,et al.Effects of different local moxibustion-like stimuli at zusanli(ST36)and zhongwan(CV12)on gastric motility and its underlying receptor mechanism[J].Evid Based Complement Alternat Med,2015,20:1-8.
7 Hofmann NA,Barth S,Waldeck-Weiermair M,et al.TRPV1mediates cellular uptake of anandamide and thus promotes endothelial cell proliferation and network-formation[J].Biol Open,2014,3:1164-1172.
8 Evangelista S.Capsaicin receptor as target of calcitonin generelated peptide in the gut[J].Prog Drug Res,2014,68:259-76.
9 Magierowski M,Jasons K,Sliwowski Z,et al.Exogenous asymmetric dimethylargigine(ADMA)in pathogenesis of ischemia-reperfusion-induced gastric lesions:interaction with protective nitric oxide(NO)and calcitionin gene-related peptide(CGRP)[J].Int J Mol Sci,2014,15:4946-4964.
10 Tanigawa T,Ahluwalia A,Watanabe T,et al.Nerve growth factor injected into the gastric ulcer base incorporates into endothelial,neuronal,glial and epithelial cells:implications for angiogenesis,mucosal regeneration and ulcer healing[J].J Physiol Pharmacol,2015,66:617-621.
11 Okumi H,Tashima K,Matsumoto K,et al.Dietary agonists of TRPV1 inhibit gastric acid secretion in mice[J].Planta Medica,2012,78:1801-1806.
12 Mózsik.Capsaicin as new orally applicable gastroprotective and therapeutic drug alone or in combination with nonsteroidal anti Inflammatory drugs inhealthy human subjects and in patients[J].Prog Drug Res,2014,68:209-258.
13 Myren J.Gastric secretion following stimulation with histamine,histology and gastrin in man[J].Universitetforlaget Oslo,1968,90:413-428.
14 Ji P(基鹏),Jiang T(姜涛),Li Y(李羽),et al.Influence of capsaicin sensitive c fibers denervation on lung ischemiareperfusion injury[J].J Sichuan Univ:Med Sci(四川大学学报,医学版),2014,45:245-248.
15 Wang M,Jip,W,et al.TRPV1 agonist capsaicin attenuates lung ischemia reperfusion injury in rabbits[J].J Surg Res,2012,173:153-160.
16 Kogure K,Goto S,Nishimura M,et al.Mechanism of potent antiperoxidative effect of capsaicin[J].Biochim Biophys Acta,2002,1573(1):84-92.
17 Tsurugizawa T,Nogusa Y,Ando Y,et al.Different TRPV1-mediated brain responses to intragastric infusion of capsaicin and capsiate[J].Eur J Neurosci,2013,38:3628-3635.