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槐果碱的镇痛、抗炎作用及其对COX-2/PGE2信号通路的影响
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| 篇名： | 槐果碱的镇痛、抗炎作用及其对COX-2/PGE2信号通路的影响 |
| TITLE： | |
| 摘要： | 目的：研究槐果碱（SC）对炎性痛模型小鼠的镇痛、抗炎作用及环氧化酶2/前列腺素E2（COX-2/PGE2）信号通路的影响。方法：（1）镇痛实验。将50只小鼠随机分为空白对照组（生理盐水）、阳性对照组（阿司匹林，100 mg/kg）和槐果碱高、中、低剂量组（40、20、10 mg/kg），每组10只，每天灌胃给药1次，连续给药5 d；末次给药后2 h，各组小鼠腹腔注射冰醋酸溶液，记录小鼠15 min内的扭体次数；另取50只小鼠，分组及给药同上，采用智能热板仪测定末次给药15、30、60、120 min后小鼠的反应痛阈值（Tr）。（2）抗炎及机制实验。取60只小鼠随机分为空白对照组（生理盐水）、模型对照组（生理盐水）、阳性对照组（阿司匹林，100 mg/kg）及槐果碱高、中、低剂量组（40、20、10 mg/kg），每组10只，每天灌胃给药1次，连续给药5 d；末次给药后60 min，除空白对照组外，其余各组小鼠均注射1％角叉菜胶致炎，并于致炎1、3、5 h后测定各组小鼠足趾肿胀度。另取60只小鼠随机分为空白对照组（生理盐水）、模型对照组（生理盐水）、槐果碱组（40 mg/kg），每组10只，每天灌胃给药1次，连续给药5 d；末次给药后60 min，除空白对照组外，其余各组小鼠均注射1％角叉菜胶致炎，5 h后采用生化法检测各组小鼠足趾肿胀组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、总抗氧化能力（T-AOC）水平；采用酶联免疫吸附试验（ELISA）检测足趾肿胀组织中PGE2水平；分别采用逆转录-聚合酶链式反应法（RT-PCR）和Western blot法测定小鼠足趾肿胀组织中COX-1、COX-2 mRNA和蛋白表达水平。结果：在镇痛实验中，与空白对照组比较，各给药组小鼠扭体次数均明显减少（P＜0.05或P＜0.01），末次给药30、60、120 min后Tr值明显升高（P＜0.05或P＜0.01）。在抗炎及机制实验中，与空白对照组比较，模型对照组小鼠致炎1、3、5 h后的足趾肿胀度明显升高（P＜0.01），足趾肿胀组织中SOD、GSH-Px、T-AOC水平明显降低（P＜0.01），MDA、PGE2水平明显升高（P＜0.01），COX-2 mRNA和蛋白表达水平明显升高（P＜0.01）；与模型对照组比较，阳性对照组和槐果碱高、中剂量组小鼠致炎3、5 h后的足趾肿胀度明显降低（P＜0.05或P＜0.01），槐果碱组小鼠足趾肿胀组织中SOD、GSH-Px、T-AOC水平明显升高（P＜0.05或P＜0.01），MDA、PGE2水平明显降低（P＜0.01），COX-2 mRNA和蛋白表达水平明显降低（P＜0.05），其他指标差异无统计学意义（P＞0.05）。结论：槐果碱具有较好的抗炎、镇痛作用，其作用机制可能与其抗氧化应激和抑制COX-2/PGE2信号通路有关。 |
| ABSTRACT： | OBJECTIVE： To study analgesic and anti-inflammatory effects of sophocarpine （SC） on inflammatory pain model mice and related COX-2/PGE2 signaling pathway. METHODS： （1）Analgesic experiment. Totally 50 mice were randomly divided into blank control group （normal saline）， positive control group （aspirin， 100 mg/kg） and SC high-dose， medium-dose and low-dose groups （40， 20， 10 mg/kg）， with 10 mice in each group. They were given relevant medicine once a day intragastrically for consecutive 5 d. 2 h after last medication， mice in each group was given glacial acetic acid solution intraperitoneal injection； writhing times of mice within 15 minutes were recorded. Other 50 mice were collected； they were grouped and given medicine as above. The response pain threshold （Tr） of mice was determined by intelligent hot plate instrument 15， 30， 60， 120 min after last administration. （2）Anti-inflammatory and mechanism experiment. Other 60 mice were randomly divided into blank control group （normal saline）， model control group （normal saline）， positive control group （aspirin， 100 mg/kg）， SC high-dose， medium-dose and low-dose groups （40， 20， 10 mg/kg）， with 10 mice in each group； they were given relevant medicine intragastrically， once a day， for consecutive 5 d. 60 min after last medication， except for blank control group， other groups were given 1％ carrageenan to induce inflammation. 1， 3， 5 h after inducing inflammation， the degree of paw swelling were determined in each group. Other 30 mice were randomly divided into blank control group （normal saline）， model control group （normal saline）， SC group （40 mg/kg）， with 10 mice in each group； they were given relevant medicine intragastrically once a day， for consecutive 5 d. 60 min after last medication， except for blank control group， other groups were given 1％ carrageenan to induce inflammation in other groups. 5 h later， the levels of SOD， MDA， GSH-Px and T-AOC in paw swelling tissue of mice were determined by biochemical method. The level of PGE2 in paw swelling tissue was determined by ELISA. The mRNA and protein expressions of COX-1 and COX-2 in paw swelling tissue of mice were detected by RT-PCR and Western blot method. RESULTS： In analgesic experiment， compared with blank control group， writhing times of mice were decreased significantly in administration groups （P＜0.05 or P＜0.01）， Tr were increased significantly 30， 60， 120 min after last medication （P＜0.05 or P＜0.01）. In anti-inflammatory and mechanism experiment， compared with blank control group， the degree of paw swelling were increased significantly in model control group 1， 3， 5 h after inducing inflammation （P＜0.01）； the levels of SOD， GSH-Px and T-AOC in paw swelling tissue were decreased significantly （P＜0.01）； the levels of MDA and PGE2 were increased significantly （P＜0.01）， and mRNA and protein expressions of COX-2 were increased significantly （P＜0.01）. Compared with model control group， the degree of paw swelling were decreased significantly in positive control group， SC high-dose and low-dose groups 3 and 5 h after inducing inflammation （P＜0.05 or P＜0.01）. The levels of SOD， GSH-Px and T-AOC in paw swelling tissue were increased significantly in SC group （P＜0.05 or P＜0.01）， while the levels of MDA and PGE2 were decreased significantly （P＜0.01） as well as mRNA and protein expressions of COX-2 were decreased significantly （P＜0.05）. There was no statistical significance in other indexes （P＞0.05）. CONCLUSIONS： SC possesses good anti-inflammatory and analgesic effects， and its mechanism may be related to anti-oxidative stress and inhibition of COX-2/PGE2 signaling pathway. |
| 期刊： | 2019年第30卷第13期 |
| 作者： | 付聪敏，王敏，徐松涛，金少举 |
| AUTHORS： | FU Congmin，WANG Min，XU Songtao，JIN Shaoju |
| 关键字： | 槐果碱；氧化应激；环氧化酶2；前列腺素E2；小鼠 |
| KEYWORDS： | Sophocarpine； Oxidative stress； COX-2； PGE2； Mice |
| 阅读数： | 822 次 |
| 本月下载数： | 16 次 |
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