不同鼠龄胶原诱导性关节炎大鼠模型差异及加味芍甘附子汤的作用和安全性分析

Difference between CIA Rat Models of Different Ages and Intervention Effect and Safety of Modified Shaoganfuzi Decoction

目的探讨不同鼠龄胶原诱导性关节炎(collagen-induced arthritis,CIA)模型的差异,并研究加味芍甘附子汤对炎性细胞因子表达的影响及其安全性。方法将青年和老年鼠各40只,随机分为正常组、模型组、对照组及中药组各4组。除正常组外,其余各组均建立CIA模型,建模后灌胃干预4周。观察大鼠一般情况,测量足踝排水体积,评价炎症指数(arthritis index,AI),末次给药取材后计算脏器指数,并检测细胞因子和安全性指标。结果造模第3周,老年模型组右足排水体积高于青年模型组(P<0.05),造模第2~4周,老年模型组AI评分均高于青年组(P<0.05);老年正常组、模型组及对照组胸腺指数均低于青年各组(P<0.01);老年中药组γ-干扰素(INF-γ)、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素17A(IL-17A)及肿瘤坏死因子-α(TNF-α)水平均低于模型组(P<0.05);老年中药组IL-17A低于对照组(P<0.05);青年中药组TNF-α、IL-6、IL-17A及肌酐(CREA)水平均低于模型组和对照组(P<0.05);老年和青年中药组谷丙转氨酶(ALT)均低于对照组(P<0.05);老年和青年中药组肌酸激酶同工酶(CK-MB)和肌钙蛋白I(c Tn I)均低于模型组和对照组(P<0.05)。结论不同鼠龄CIA大鼠关节炎症程度存在差异,加味芍甘附子汤安全有效,衰老引起的胸腺退化可能是引起老年期发病类风湿关节炎(EORA)与青壮年发病类风湿关节炎(YORA)差异的原因之一。

Objective To investigate the difference between collagen-induced arthritis(CIA)models of rats of different ages,and to study the effect of modified Shaoganfuzi decoction on the expression of inflammatory cytokines and its safety.Methods Forty young rats and forty old rats were randomly divided into four groups:the normal group,model group,control group and TCM group.Except the normal group,CIA models were established in all the other groups,and intragastric intervention was performed for 4 weeks after modeling.The conditions of the rats were observed,the drainage volume of the ankle was measured,the inflammation index(AI)was evaluated,the organ index after the last administration was calculated,and cytokines and safety indicators were detected.Results In the third week of modeling,the drainage volume of right feet in the elder model group was higher than that in the young model group(P<0.05).Two to four weeks into modeling,the AI scores of the elder model group were higher than those in the young group(P<0.05).The thymus indexes of the normal group,model group and control group were lower than those of the young group(P<0.01).Levels of γ-interferon(INF-γ),interleukin-2(IL-2),interleukin-6(IL-6),interleukin 17 A(IL-17 A)and tumor necrosis factor-α(TNF-α)in the elder TCM group were lower than in the model group(P<0.05).The level of IL-17 A in the elder TCM group was lower than in the control group(P<0.05).The levels of TNF-α,IL-6,IL-17 A and creatinine(CREA)in the young TCM group were lower than in the model group and the control group(P<0.05).Levels of alanine aminotransferase(ALT)in the elder and young TCM groups were lower than in the control group(P<0.05).Levels of creatine kinase isoenzyme(CK-MB)and troponin I(cTnI)in both the elder and young TCM groups were lower than in the model group and control group(P<0.05).Conclusion There are differences in the severity of joint inflammation between CIA rats of different ages.The modified Shaoganfuzi decoction is safe and effective.Thymus degeneration caused by ageing may account for the difference between EORA and YORA.