免疫激动剂和抑制剂对CCI大鼠热痛敏的影响

Association of Immunization and Thermal Latencies in Rats with Chronic Constriction Injury

目的观察慢性压榨性损伤(CCI)模型大鼠在免疫激活剂脂多糖(LPS)和免疫抑制剂环孢素A(cyclosporin,CsA)作用下大鼠热痛敏是否改变,并观察免疫调节剂是否通过中枢神经系统小胶质细胞的活化影响大鼠的热耐受时间。方法雄性SD大鼠36只随机分为生理盐水(NS)组、LPS组和CsA组,每组12只,采用轻轻结扎一侧坐骨神经主干建立CCI大鼠模型。造模术后第3 d,按其分组分别给予不同干预(NS 2 mL、LPS 1 mg/kg,CsA6 mg/kg,腹腔注射,每天1次)。分别在CCI术前(当天)和术后3、5、7、10、13、14 d测定大鼠手术侧和对侧热刺激-缩足时间和触诱发痛针刺-缩足强度。造模后2周处死大鼠,取脊髓L4节段并制成切片,用免疫组化方法观察免疫调节剂作用下CD11b阳性小胶质细胞的分布和形态变化。结果成功建立CCI大鼠模型。LPS组热刺激-缩足时间缩短,CsA组热刺激-缩足时间延长。LPS组和NS组在脊髓L4节段的灰、白质中均可见大量活化的小胶质细胞,CsA组在脊髓L4节段则有较多正常形态的小胶质细胞。结论免疫调节剂能影响CCI大鼠的热痛敏,且这种影响可能与小胶质细胞有关。

Objective To observe the change of thermal latencies,spinal cord morphology and quantity of microglia following the treatment of lipopolysaccharide（LPS） or cyclosporin A（CsA） in rats with established neuropathic pain through chronic constriction injury（CCI）.Methods A total of 36 male SD rats with CCI of sciatic nerve were randomly divided into LPS group,CsA group and NS group,and injected with LPS（1 mg/kg）,CsA（6 mg/kg）,and NS（2 mL） per day respectively since the 3rd day post operation.The thermal latencies and mechanical thresholds of the rats were measured preoperatively and on the 3^rd,5^th,7^th,10^th,13^th and 14^th day post operation.The rats were sacrificed on the 14th day and the L4 of spinal cords were harvested for CD11b IHC examination of microglia.Results The thermal latencies went down steadily in rats treated with LPS,but went up in rats treated with CsA since the 3rd day after nerve injury.More active microglia were found in the white and grey matter of the spinal cord L4 in rats treated with LPS and NS than in rats treated with CsA.The majority of microglia were inactive in rats treated with CsA.Conclusion Immunomodulator might affect the thermal latencies of CCI rat model,perhaps through microglia in the central nerve system.