摘要
目的 探讨炎性痛大鼠背根神经节趋化因子受体2（CCR2）与p38丝裂原活化蛋白激酶（p38MAPK）信号通路的关系,进一步明确炎性痛的发生机制.方法 健康雌性SD大鼠72只,体重150 - 180 g,3-4月龄,采用随机数字表法分为3组（n=24）：对照组（C组）于右后足底注射生理盐水100 μl;炎性痛组（IP组）于右后足底注射完全弗氏佐剂100μl; CCR2抑制剂RS102895组（RS组）于右后足底注射完全弗氏佐剂100μl,同时腹腔注射RS102895 20mg/kg,连续7d,1次/d.于注药前与注药后1、3、5、7d测定右后足底机械缩足反应阈（MWT）.于注药后3、5、7d随机取8只大鼠,采用免疫组化法测定背根神经节CCR2与磷酸化p38MAPK （p-p38MAPK）的表达水平,RT-PCR法测定CCR2与p38MAPK的mRNA表达水平.结果 与C组比较,IP组和RS组注药后各时点MWT降低,背根神经节CCR2和p-p38MAPK阳性细胞计数和免疫组化染色评分升高,CCR2和p38MAPK的mRNA表达均上调（P＜0.05）;与iP组比较,RS组注药后各时点MWT升高,背根神经节CCR2和p-p38MAPK阳性细胞计数和免疫组化染色评分降低,CCR2和p38MAPK的mRNA表达均下调（P＜0.05）.结论 背根神经节CCR2可能通过激活p38MAPK信号通路参与了大鼠炎性痛的发生.
Objective To investigate the relationship between C-C chemokinereceptor type 2 （CCR2） and p38 mitogen-activated protein kinase （p38MAPK） signaling pathway in the dorsal root ganglion of rats and further clarify the mechanism of inflammatory pain.Methods Sevemy-two female Sprague-Dawley rats,weighing 150-180 g,aged 3-4 months,were randomly divided into 3 groups （n =24 each） using a random number table：control group （group C）,inflammatory pain group （IP group） and CCR2 inhibitor RS102895 group （group RS）.Inflammatory pain was induced by subcutaneous injection of Freund＇s adjuvant 100μl into the plantar surface of the right hindpaw.RS102895 20 mg/kg was injected subcutaneously once a day for 7 consecutive days in addition to Freund＇s adjuvant in group RS.Mechanical paw withdrawal threshold （MWT） was measured before injection and at 1,3,5 and 7 days after injection.At 3,5 and 7 days after injection,8 rats in each group were sacrificed and the dorsal root ganglions were removed for determination of the expression of CCR2 and phosphor-p38MAPK （p-p38MAPK） （by immuno-histochemical staining）,and CCR2 and p38MAPK mRNA （using fluorescent quantitative PCR）.Immuno-histochemical staining was scored.Results Compared with group C,MWT was significantly decreased after injection,the number of p-p38MAPK positive neurons and immuno-histochemical staining score were increased,and CCR2 and p38MAPK mRNA expression was up-regulated in IP and RS groups.Compared with group IP,MWT was significantly increased after injection,the number of p-p38MAPK positive neurons and immuno-histochemical staining score were decreased,and CCR2 and p3gMAPK mRNAexpression was down-regulated in RS group.Conclusion CCR2 in the dorsal root ganglion is involved in the development of inflammato pain possibility through activating p38MAPK signaling pathway in rats.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2014年第12期1460-1463,共4页
Chinese Journal of Anesthesiology
