身痛逐瘀汤对CIA模型大鼠预防及治疗的作用研究

Preventive and therapeutic effect of Shentong Zhuyu decoction on CIA model rats

目的 探究身痛逐瘀汤对胶原诱导Lewis大鼠关节炎模型(CIA模型)大鼠的预防效果及治疗作用。方法 将42只大鼠随机分为空白组,模型组,甲氨蝶呤组(0.9 mg·kg^(-1)),预防给药组(身痛逐瘀汤,9 g·kg^(-1)),身痛逐瘀汤低(4.5 g·kg^(-1))、中(9 g·kg^(-1))、高(18g·kg^(-1))剂量组,每组6只,除空白组外,其余各组使用胶原对Lewis大鼠进行二次免疫构建CIA模型。实验中每周两次记录动物状态、关节炎评分、足容积及痛阈值,实验终点检测大鼠血液流变学变化,使用ELISA法测定大鼠血清中IL-10、TGF-β、IL-17、TNF-α、MMP1、MMP13、RANKL的表达,使用HE染色、番红固绿染色观察其踝关节组织的病理变化并进行组织病理学评分。结果 与模型组相比,身痛逐瘀汤各剂量组的关节炎评分、痛阈值、足肿胀率均降低,其中身痛逐瘀汤中、高剂量组效果显著;身痛逐瘀汤中、高剂量组的低、中、高切全血黏度,血浆黏度、血沉及血沉方程K值显著降低;各剂量组促进抑炎因子IL-10的表达升高,促炎因子TGF-β、IL-17、TNF-α的表达降低,抑制骨损伤相关炎症因子MMP-1、MMP-13、RANKL的含量,减轻病理损伤,高剂量组治疗效果显著;身痛逐瘀汤预防给药组在大鼠关节炎评分、痛阈值、足肿胀率、血清炎症因子及病理切片的结果均优于身痛逐瘀汤各治疗剂量组。结论 身痛逐瘀汤对CIA模型大鼠具有良好的预防效果及治疗作用,可以有效缓解大鼠的关节炎症状,减轻疼痛,改善血液流变,抑制炎症,改善病理损伤。

Objective To determine the preventive and therapeutic effect of Shentong Zhuyu decoction on collagen-induced Lewis rat arthritis model(CIA model)rats.Methods Totally 42 rats-were randomly divided into a blank group,a model group,a methotrexate group(0.9 mg·kg^(-1)),-a preventive administration group(Shentong Zhuyu decoction,9 g·kg^(-1)),and Shentong Zhuyu-decoction low-(4.5 g·kg^(-1)),medium-(9 g·kg^(-1)),high-(18 g·kg^(-1))dose groups,with 6 rats in each group.Except for the blank group,the CIA model of Lewis rats was constructed by using collagen for secondary immunization in other groups.During the experiment,animal status,arthritis score,foot volume and pain threshold were recorded twice a week.The changes in hemorheology were detected at the end point of the experiment.The expressions of IL-10,TGF-β,IL-17,TNF-α,MMP1,MMP13 and RANKL in the serum of rats were determined by enzyme-linked immunosorbent assay.The pathological changes and histopathological scores of the ankle joint were observed by HE staining and safranin-fast green staining.Results Compared with the model group,the arthritis scores,pain thresholds,and foot swelling rates in each dose groups of Shentong Zhuyu decoction were all reduced,among which the medium-and high-dose groups of Shentong Zhuyu decoction had more significant effect.The low,medium and high shear whole blood viscosity,plasma viscosity,erythrocyte sedimentation rate and erythrocyte sedimentation rate equation K value in the medium-and high-dose treatment groups were greatly reduced.The content of anti-inflammation factor IL-10 increased in each dose treatment group,and the expression of the pro-inflammatory factors TGF-β,IL-17,and TNF-α,and inhibited the expression of bone damage-related serum inflammatory factors MMP-1,MMP-13,and RANKL all inhibited.Reduction of pathological damage was obvious in the high-dose group.In the Shentong Zhuyu decoction preventive administration group,the arthritis scores,pain thresholds,foot swelling rates,serum inflammatory factors and pathological sections were all better than those in the Shentong Zhuyu decoction therapeutic dose groups.Conclusion Shentong Zhuyu decoction has good preventive and therapeutic effect on CIA models rats,which effectively alleviate arthritis symptoms,reduce pain,improve blood rheology,inhibit inflammation and reduce pathological damage in rats.