不同剂量四神煎对胶原诱导性关节炎大鼠炎性细胞因子及肝肾功能的影响

Influence of different doses of Sishen Decoction on the inflammatory cytokines, the liver and kidney function of collagen-induced arthritis rats

目的:观察不同剂量四神煎对胶原诱导性关节炎大鼠炎性细胞因子及肝肾功能的影响,研究其疗效和安全性,为"基于汗法治痹"的临床应用提供参考。方法:Wistar大鼠(雌性,60只),随机分为6组:正常组、模型组、雷公藤多苷组及四神煎大、中、小剂量组,每组10只。正常组常规饲养。其余各组复制胶原诱导性关节炎(CIA)大鼠模型后分别以蒸馏水、雷公藤多苷及不同剂量四神煎干预4周,观察CIA大鼠关节肿胀、血清炎性细胞因子、肝肾功能(包括肝肾早期损伤指标)的变化。结果:四神煎各剂量组及雷公藤多苷组较模型组关节炎指数(AI)显著降低(P<0.05);与正常组比较,模型组TNF-α、IL-1β、ALT水平显著升高(P<0.05),Cre水平显著降低(P<0.05);与模型组相比,各治疗组均不同程度降低TNF-α、IL-1β、ALT、AST水平,且四神煎大剂量组优于四神煎中、小剂量组(P<0.05)。各治疗组能够显著降低升高的α-GST、PNP、OCT、NGAL、Cyst C水平,且四神煎大剂量组降低α-GST、OCT、NGAL水平显著优于雷公藤多苷组、中剂量组、小剂量组间(P<0.05),降低PNP、Cyst C水平与雷公藤多苷组相当,优于中、小剂量组(P<0.05);TBA水平在各间差异无统计学意义。结论:汗法治痹理论指导下,大剂量应用黄芪为特点的四神煎原方能够有效抑制CIA大鼠炎症细胞因子,减轻关节肿胀,且能够改善CIA大鼠异常的肝肾功能,为临床应用提供依据。

Objective： To observe the influence of different doses of Sishen Decoction on the inflammatory cytokines, the liver and kidney function of collagen-induced arthritis rats to study the curative effect and the safety of it, which will provide reference for the clinical application of sweating treatment arthralgia. Methods： 60 female Wistar rats were randomly divided into 6 groups： normal group, model group, tripterygium glycosides group （control group）, high, medium and small dose groups of Sishen decoction, 10 rats in each group. The normal group were given conventional breeding. The other groups were made collagen induced arthritis （CIA） rat models and gavaged with distilled water, tripterygium glycosides and different doses of Sishen Decoction respectively for 4 weeks, then the changes of the joint swelling, levels of serum inflammatory cytokines, liver and kidney function （including liver and kidney early injury indicators） of CIA rats were observed. Results： The arthritis index decreased obviously in each dose group of Sishen Decoction and tripterygium glycosides group than model group （P〈0.05）, but there was no statistically significant difference between the groups. Compared with normal group, the level of TNF-α, IL-1 β, ALT increased and Cre decreased in model group （P〈0.05）. Compared with model group, the level of TNF-α, IL-113, ALT, AST decreased in the treatment groups, and high dose group of Sishen Decoction was better than medium and small dose group of Sishen Decoction （P〈0.05）. The treatment group could significantly reduce the level of a-GST, PNP, OCT, NGAL, and Cre increased Cyst C, and high dose group of Sishen Decoction could significantly reduce the levels of α -GST, OCT, NGAL than medium and small dosegroup of Sishen Decoction and tripterygium glycosides group （P〈0.05）. The high-dose group of Sishen Decoction was the same as tripterygium group to reduce the levels of PNP, Cyst C （P〈0.05）, and was better than the medium and small dose group of Sishen Decoction （P〈0.05）. There was no statistically significant difference between each group in the level of TBA. Conclusion： Sishen Decoction original prescription based on application of high dose of astragalus root characteristics, under the theoretical guidance of sweating treatment arthralgia, could effectively inhibit the CIA rat inflammatory cytokines, reduce swelling in the joints, and could improve the abnormal function of liver and kidney of CIA rats, which will provide the basis for clinical application.