基于脂代谢和炎症反应探讨两种湿热证痛风性关节炎大鼠模型的构建

Establishment of two rat models of gouty arthritis with damp-heat syndrome based on lipid metabolism and proinflammatory factors

目的比较两种不同湿热证GA大鼠模型在脂代谢和炎症反应的差异,以探索安全、稳定、可重复性高的湿热证GA模型。方法44只SD大鼠随机分为正常对照组(n=10)、GA对照组(n=10)、模型组A(n=12)和模型组B(n=12)。观察造模期间各组大鼠一般情况及死亡率;周长法测定踝关节肿胀度;酶联免疫吸附(ELISA)法检测血清脂代谢(TG、TC、LDL-C、HDL-C)和炎症因子(NF-κB、IL-1β、TNF-α、IL-6)。结果模型组A死亡率8.3%(1/12),模型组B死亡率25%(3/12);与正常对照组和GA对照组比较,模型组A和模型组B血清TG、TC和LDL-C表达显著升高(P<0.01),而HDL-C表达显著降低(P<0.01);与模型组A相比,模型组B的TG和HDL-C趋势有所升高,TC和LDL-C趋势降低,但无统计学意义(P>0.05)。与正常对照组比较,GA对照组、模型组A和模型组B的NF-κB、IL-1β、IL-6和TNF-α表达显著升高(P<0.01);与GA对照组比较,模型组A的NF-κB和TNF-α表达有所升高(P<0.05),模型组B的NF-κB、IL-1β、IL-6和TNF-α表达有所升高(P<0.05);与模型组A比较,模型组B的IL-1β、IL-6和TNF-α表达有所升高(P<0.05)。结论两种方式均可成功诱导湿热证GA病证结合模型。二者既有共性也有各自特点,高脂高糖饮食是脂代谢紊乱的直接影响因素,生物因子较单纯的高温高湿环境对大鼠炎症影响更明显。

Objective To explore a safe,stable and repeatable model of gouty arthritis(GA)with damp-heat syndrome by comparing changes in lipid metabolism and proinflammatory factors between two rat models of GA with damp-heat.Methods Overall,44 male SD rats were randomly divided into a control group(n=10),GA group(n=10),model group A(n=12)and model group B(n=12).The specific method was provided in full text,and the experimental period lasted for 21 days.The general condition of rats in each group was observed during the modeling period and the mortality rate was assessed after modeling.Ankle swelling was measured by the circumference method.Serum contents of lipid metabolism factors(TG,TC,LDL-C and HDL-C)and proinflammatory factors(NF-κB,IL-1β,TNF-αand IL-6)were determined by ELISA.Results The mortality rate was 8.3%(1/12)in model group A and 25%(3/12)in model group B.Compared with control and GA groups,the serum TG,TC,and LDL-C were significantly higher in the model group A and B(P<0.01),while HDL-C was decreased significantly(P<0.01).Compared with model group A,TG and HDL-C were increased in the model group B,while TC and LDL-C were decreased,but without statistical significance(P>0.05).Compared with the control group,serum NF-κB,IL-1β,IL-6 and TNF-αwere significantly higher in the GA group,and model group A and B(P<0.01).Compared with the GA group,NF-κB and TNF-αwere increased in the model group A(P<0.05),and NF-κB,IL-1β,IL-6 and TNF-αwere increased in model group B(P<0.05).Compared with model group A,IL-1β,IL-6 and TNF-αwere increased in model group B(P<0.05).Conclusions Both approaches successfully induced a combined model of GA with damp-heat syndrome.Both of them had commonalities and individualities.The high fat and sugar diet was a directly influencing factor for lipid metabolism disorder.Biological factors had more obvious effects on inflammation in rats than a high temperature and humidity environment.