舒芬太尼预先给药对浸水束缚应激大鼠胃组织ASIC3表达的影响
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摘要
目的观察舒芬太尼与APETx2预先给药对浸水束缚应激(WIRS)大鼠胃组织酸敏感离子通道3(ASIC3)表达及胃黏膜损伤的影响。方法 40只雄性Wistar大鼠随机等分为对照组(C组)、应激组(W组)、舒芬太尼预先给药组(S组,腹腔内注射舒芬太尼25μg/kg)及ASIC3特异性拮抗剂APETx2预先给药组(A组,腹腔内注射APETx2 25μg/kg)。采用WIRS法复制应激性胃黏膜损伤模型,于应激6 h后留取标本测定溃疡指数(UI);黄嘌呤氧化酶法测定胃组织超氧化物歧化酶(SOD)活力与硫代巴比妥酸法测定丙二醛(MDA)含量;免疫组化和免疫印迹法测定胃组织ASIC3蛋白表达。结果与C组比较,W组、S组及A组的UI值显著升高(P均<0.01),SOD值显著下降(P均<0.01),MDA值显著升高(P均<0.01),胃组织ASIC3蛋白表达显著上调(P均<0.01)。与W组比较,S组及A组的UI值显著下降(P均<0.01),SOD值显著升高(P均<0.01),MDA值显著下降(P均<0.01);A组的ASIC3蛋白表达显著下调(P<0.01),S组差异无统计学意义(P>0.05)。结论 APETx2调控胃组织ASIC3蛋白表达,逆转氧自由基代谢失衡起胃黏膜保护作用;舒芬太尼同样通过逆转氧自由基代谢失衡起胃黏膜保护作用,但其作用机制并非通过调控ASIC3完成。
Objective To evaluate the effects of pretreatments of sufentanil and APETx2 on acid sensing ion channel 3( ASIC3) expression in stomach tissues of rats with water immersion restraint stress( WIRS) and gastric mucosal injury.Methods Forty male Wistar rats were randomly assigned to four groups( n = 10 each) : control group( group C),stress group( group W),sufentanil pretreatment group( group S,intraperitoneal injection of 25 μg / kg sufentanil),APETx2 pretreatment group( group A,intraperitoneal injection of 25 μg / kg APETx2). The stress-induced gastric mucosal injury model was established by WIRS method. Six hours after stress,the gastric tissues specimen was taken to detect the ulcer index( UI),the total activity of superoxide dismutase( SOD) in gastric tissues by xanthine oxidase method,the content of malondialdehyde( MDA) in gastric tissues by thiobarbituric acid( TBA) method and ASIC3 protein expression in gastric tissues by immunohistochemistry and immunoblotting methods. Results Compared with group C,in groups W,S and A,the UI value increased significantly( all P < 0. 01); the SOD level decreased significantly( all P < 0. 01); the MDA level increased significantly( all P < 0. 01); ASIC3 protein expression in gastric tissues was up-regulated significantly( all P < 0. 01). Compared with group W,in groups S and A,the UI value decreased significantly( all P < 0. 01); the SOD level increased significantly( all P < 0. 01); MDA level decreased significantly( all P < 0. 01); ASIC3 protein expression was down-regulated significantly in group A( P < 0. 01),and there was no significant difference in ASIC3 protein expression between groups W and S( P > 0. 05). Conclusions APETx2 can play a protective role on gastric mucosa by regulating ASIC3 protein expression in gastric tissues and reversing the imbalance of oxygen free radical metabolism,while sufentanil can also play a protective role on gastric mucosa by reversing the imbalance of oxygen free radical metabolism,but its mechanism may not be through regulation of ASIC3.
Objective To evaluate the effects of pretreatments of sufentanil and APETx2 on acid sensing ion channel 3( ASIC3) expression in stomach tissues of rats with water immersion restraint stress( WIRS) and gastric mucosal injury.Methods Forty male Wistar rats were randomly assigned to four groups( n = 10 each) : control group( group C),stress group( group W),sufentanil pretreatment group( group S,intraperitoneal injection of 25 μg / kg sufentanil),APETx2 pretreatment group( group A,intraperitoneal injection of 25 μg / kg APETx2). The stress-induced gastric mucosal injury model was established by WIRS method. Six hours after stress,the gastric tissues specimen was taken to detect the ulcer index( UI),the total activity of superoxide dismutase( SOD) in gastric tissues by xanthine oxidase method,the content of malondialdehyde( MDA) in gastric tissues by thiobarbituric acid( TBA) method and ASIC3 protein expression in gastric tissues by immunohistochemistry and immunoblotting methods. Results Compared with group C,in groups W,S and A,the UI value increased significantly( all P < 0. 01); the SOD level decreased significantly( all P < 0. 01); the MDA level increased significantly( all P < 0. 01); ASIC3 protein expression in gastric tissues was up-regulated significantly( all P < 0. 01). Compared with group W,in groups S and A,the UI value decreased significantly( all P < 0. 01); the SOD level increased significantly( all P < 0. 01); MDA level decreased significantly( all P < 0. 01); ASIC3 protein expression was down-regulated significantly in group A( P < 0. 01),and there was no significant difference in ASIC3 protein expression between groups W and S( P > 0. 05). Conclusions APETx2 can play a protective role on gastric mucosa by regulating ASIC3 protein expression in gastric tissues and reversing the imbalance of oxygen free radical metabolism,while sufentanil can also play a protective role on gastric mucosa by reversing the imbalance of oxygen free radical metabolism,but its mechanism may not be through regulation of ASIC3.
引文
[1]解立俊,屠伟峰.颅脑损伤后应激性胃粘膜病变的病理生理机制研究进展[J].实用医学杂志,2007,23(6):920-922.
[2]郄文斌,屠伟峰,温君琳,等.冷水束缚应激对大鼠脊髓背根神经节、胃组织内TRPV1 mRNA及血清SOD、MDA的影响[J].广东医学,2014,35(16):2506-2510.
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[4]徐少群,屠伟峰,郄文斌,等.APETx2对应激性胃黏膜损伤大鼠脊髓背根神经节酸敏感离子通道3表达的影响[J].实用医学杂志,2015,31(7):1088-1091.
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[7]Xu S,Tu W,Wen J,et al.The selective ASIC3 inhibitor APETx2 alleviates gastric mucosal lesion in the rat[J].Pharmazie,2014,69(7):542-546.
[8]Lim JH,Kim JH,Kim N,et al.Gastroprotective effect of cochinchina momordica seed extract in nonsteroidal anti-inflammatory drug-induced acute gastric damage in a rat model[J].Gut Liver,2014,8(1):49-57.
[9]Ali T,Harty RF.Stress-induced ulcer bleeding in critically ill patients[J].Gastroenterol Clin North Am,2009,38(2):245-265.
[10]丁冬,屠伟峰,李成龙.氯胺酮预处理对大鼠应激性溃疡的保护作用[J].实用医学杂志,2008,24(2):179-181.
[11]凌琼,屠伟峰,李成龙,等.氟比洛芬酯预处理明显减轻冷水束缚应激大鼠氧自由基介导性急性胃黏膜损害[J].国际麻醉学与复苏杂志,2009,30(2):116-118.
[12]李成龙,屠伟峰,丁冬.舒芬太尼预处理对大鼠急性胃黏膜病变组织中TNF-a mRNA与IL-1βmRNA表达的影响[J].热带医学杂志,2010,10(6):663-665.
[13]Holzer P.Role of visceral afferent neurons in mucosal inflammation and defense[J].Curr Opin Pharmacol,2007,7(6):563-569.
[14]Jensen JE,Durek T,Alewood PF,et al.Chemical synthesis and folding of APETx2,a potent and selective inhibitor of acid sensing ion channel 3[J].Toxicon,2009,54(1):56-61.
[15]Bulsiewicz WJ,Shaheen NJ,Hansen MB,et al.Effect of amiloride on experimental acid-induced heartburn in non-erosive reflux disease[J].Dig Dis Sci,2013,58(7):1955-1959.
[16]Izumi M,Ikeuchi M,Ji Q,et al.Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis[J].J Biomed Sci,2012,19(1):77.
[17]Yuan FL,Chen FH,Lu WG,et al.Acid-sensing ion channels 3:a potential therapeutic target for pain treatment in arthritis[J].Mol Biol Rep,2010,37(7):3233-3238.
[18]Deval E,Nol J,Gasull X,et al.Acid-sensing ion channels in postoperative pain[J].J Neurosci,2011,31(16):6059-6066.
[19]Karczewski J,Spencer RH,Garsky VM,et al.Reversal of acid-induced and inflammatory pain by the selective ASIC3 inhibitor,APETx2[J].Br J Pharmacol,2010,161(4):950-960.
[20]刘晓艳,屠伟峰,曹明,等.舒芬太尼或(和)泮托拉唑预处理对浸水束缚应激大鼠胃黏膜损伤的影响[J].实用医学杂志,2013,29(6):883-886.
[21]杨垂勋,屠伟峰,安裕文.舒芬太尼预处理对冷水束缚应激大鼠血浆促肾上腺皮质激素释放因子的影响[J].实用医学杂志,2010,26(18):3299-3301.
[2]郄文斌,屠伟峰,温君琳,等.冷水束缚应激对大鼠脊髓背根神经节、胃组织内TRPV1 mRNA及血清SOD、MDA的影响[J].广东医学,2014,35(16):2506-2510.
[3]蒋群,屠伟峰.舒芬太尼预处理对大鼠急性胃粘膜病变的保护作用及与酸敏感离子通道的关系[J].南方医科大学学报,2010,30(5):1099-1102.
[4]徐少群,屠伟峰,郄文斌,等.APETx2对应激性胃黏膜损伤大鼠脊髓背根神经节酸敏感离子通道3表达的影响[J].实用医学杂志,2015,31(7):1088-1091.
[5]Yuan LP,Bo Y,Ming G,et al.Expression of acid-sensing ion channels of gastric mucosa from patients with Henoch-Schnlein purpura[J].J Pediatr Gastroenterol Nutr,2012,54(4):561-563.
[6]Holzer P.Acid-sensing ion channels in gastrointestinal function[J].Neuropharmacology,2015,94:72-79.
[7]Xu S,Tu W,Wen J,et al.The selective ASIC3 inhibitor APETx2 alleviates gastric mucosal lesion in the rat[J].Pharmazie,2014,69(7):542-546.
[8]Lim JH,Kim JH,Kim N,et al.Gastroprotective effect of cochinchina momordica seed extract in nonsteroidal anti-inflammatory drug-induced acute gastric damage in a rat model[J].Gut Liver,2014,8(1):49-57.
[9]Ali T,Harty RF.Stress-induced ulcer bleeding in critically ill patients[J].Gastroenterol Clin North Am,2009,38(2):245-265.
[10]丁冬,屠伟峰,李成龙.氯胺酮预处理对大鼠应激性溃疡的保护作用[J].实用医学杂志,2008,24(2):179-181.
[11]凌琼,屠伟峰,李成龙,等.氟比洛芬酯预处理明显减轻冷水束缚应激大鼠氧自由基介导性急性胃黏膜损害[J].国际麻醉学与复苏杂志,2009,30(2):116-118.
[12]李成龙,屠伟峰,丁冬.舒芬太尼预处理对大鼠急性胃黏膜病变组织中TNF-a mRNA与IL-1βmRNA表达的影响[J].热带医学杂志,2010,10(6):663-665.
[13]Holzer P.Role of visceral afferent neurons in mucosal inflammation and defense[J].Curr Opin Pharmacol,2007,7(6):563-569.
[14]Jensen JE,Durek T,Alewood PF,et al.Chemical synthesis and folding of APETx2,a potent and selective inhibitor of acid sensing ion channel 3[J].Toxicon,2009,54(1):56-61.
[15]Bulsiewicz WJ,Shaheen NJ,Hansen MB,et al.Effect of amiloride on experimental acid-induced heartburn in non-erosive reflux disease[J].Dig Dis Sci,2013,58(7):1955-1959.
[16]Izumi M,Ikeuchi M,Ji Q,et al.Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis[J].J Biomed Sci,2012,19(1):77.
[17]Yuan FL,Chen FH,Lu WG,et al.Acid-sensing ion channels 3:a potential therapeutic target for pain treatment in arthritis[J].Mol Biol Rep,2010,37(7):3233-3238.
[18]Deval E,Nol J,Gasull X,et al.Acid-sensing ion channels in postoperative pain[J].J Neurosci,2011,31(16):6059-6066.
[19]Karczewski J,Spencer RH,Garsky VM,et al.Reversal of acid-induced and inflammatory pain by the selective ASIC3 inhibitor,APETx2[J].Br J Pharmacol,2010,161(4):950-960.
[20]刘晓艳,屠伟峰,曹明,等.舒芬太尼或(和)泮托拉唑预处理对浸水束缚应激大鼠胃黏膜损伤的影响[J].实用医学杂志,2013,29(6):883-886.
[21]杨垂勋,屠伟峰,安裕文.舒芬太尼预处理对冷水束缚应激大鼠血浆促肾上腺皮质激素释放因子的影响[J].实用医学杂志,2010,26(18):3299-3301.