摘要
目的 探讨蒙药森登对胶原诱导性关节炎（CIA）模型大鼠干扰素γ和白细胞介素4（IL-4）表达的影响.方法 将60只大鼠完全随机分为正常组、模型组、雷公藤多苷组[9.45 mg/（kg·d）]和蒙药森登汤低、中、高剂量组[1.35、2.70、5.40 g/（kg·d）],每组30只,采用胶原诱导方法建立大鼠免疫性关节炎模型.各治疗组于造模后第12天开始灌胃给药,正常组和模型组同期灌胃等体积蒸馏水,1次/d,疗程28 d.于造模前（0 d）、治疗前（开始造模后10 d）及治疗后（开始造模后20、30、40 d）观察大鼠一般情况、测量后足掌厚度、评估关节炎指数;疗程结束后,采用酶联免疫吸附法检测血清干扰素γ和IL-4水平,计算干扰素γ/IL-4比值,采用免疫组织化学方法检测踝关节中干扰素γ和IL-4的表达水平.结果 模型组大鼠一般情况差,各治疗组大鼠一般情况优于模型组.20、30、40 d时点雷公藤多苷组和蒙药森登汤低、中、高剂量组大鼠足掌厚度变化均低于模型组,差异有统计学意义[20d：（4.06±0.04）、（4.31±0.03）、（4.24±0.03）、（4.24 ±0.03）mm比（4.47±0.04）mm;30 d：（4.69±0.04）、（3.99±0.06）、（3.86±0.04）、（3.81±0.04）mm比（4.45±0.04）mm;40 d：（4.56±0.03）、（3.94±0.05）、（3.74 ±0.04）、（3.65±0.02）mm比（4.38±0.03）mm] （P ＜0.01）,其中雷公藤多苷组和蒙药森登汤高剂量组与蒙药森登汤低剂量组比较差异有统计学意义（P＜0.01）.20、30、40 d时点雷公藤多苷组和蒙药森登汤低、中、高剂量组大鼠关节炎指数均低于模型组,差异有统计学意义[20 d：（8.2±1.4）、（8.9±1.1）、（8.3±1.3）、（8.8±1.7）分比（10.9±1.3）分;30 d：（6.2±1.3）、（7.7±1.3）、（7.1±1.1）、（7.3±1.2）分比（9.7±1.2）分;40 d：（4.1±0.9）、（6.8±1.3）、（6.1±1.0）、（5.2±1.3）分比（8.9±0.7）分]（P＜0.05或P＜0.01）,其中雷公藤多苷组和蒙药森登汤高剂量组与蒙药森登汤低剂量组比较差异有统计学意义（P＜0.01）.模型组血清干扰素γ水平明显高于正常组[（396±30） ng/L比（238±36） ng/L],雷公藤多苷组和蒙药森登汤低、中、高剂量组干扰素γ水平均明显低于模型组[（251±36）、（323±51）、（295±24）、（258±23） ng/L比（396±30） ng/L] （P＜0.01）;各组间血清IL-4含量差异无统计学意义（P＞0.05）.模型组血清干扰素γ/IL-4明显高于正常组[（28.5±3.2）比（19.4±4.2）],雷公藤多苷组和蒙药森登汤中、高剂量组干扰素γ/IL-4明显低于模型组[（21.1±4.3）、（22.1±2.0）、（21.4±2.6）比（28.5±3.2）]（P＜0.01）.模型组踝关节干扰素γ和IL-4表达水平明显高于正常组[（8.4±2.3）分比（2.1±0.8）分,（7.5±1.2）分比（1.8±0.7）分],雷公藤多苷组和蒙药森登汤中、高剂量组干扰素γ表达水平明显低于模型组[（3.6±2.1）、（5.4±2.3）、（3.7±2.1）分比（8.4±2.3）分],雷公藤多苷组和蒙药森登汤高剂量组IL-4表达水平明显低于模型组[（2.1±0.9）、（3.8±1.4）分比（7.5±1.2）分]（P＜0.01）.结论 蒙药森登能够改善CIA模型大鼠一般情况及关节炎症状,降低干扰素γ、IL-4的表达水平,高剂量疗效与阳性对照药雷公藤多苷相当.
Objective To explore the effect of Mongolian medicine Senden decoction on expression of interferon （IFN） γ and interleukin （IL） 4 in collagen induced arthrtitis （CIA） rat model.Methods The CIA model was incuced by collagen.Sixty rats were randomly divided into normal group,model group,tripterygium glycosides group [9.45 mg/（kg · d）],Mongolian medicine low,middle and high dose group [1.35,2.70,5.40 g/（kg· d）].The therapy groups were given intragastric administration of drugs on the 12th day after establishment of CIA model （1 time/d,last for 28 d）.Before establishment of CIA model （0 d）,before therapy （10 d） and after therapy （20,30,40 d）,the general conditions of the rat were observed;the thickness of hind plantar was measured and the arthritis index was assessed.At the end of therapy,the levels of IFN-γand IL-4 in serum were measured by enzyme linked immunosorbent assay;the expressions of IFN-γ and IL-4 in the ankle joint were assessed by immunohistochemistry.Results The general conditions of the rats in model group were bad and they were improved in four therapy groups.At 20,30 and 40 d time points,the thickness of hind paw in tripterygium glycosides group,Mongolian medicine low,middle and high dose group was significantly lower than that in model group[20 d：（4.06 ±.04）,（4.31 ±.03）,（4.24 ±.03）,（4.24 ±.03） mm vs （4.47 ±0.04） mm;30 d：（4.69 ±#±0.04）,（3.99 ±.06）,（3.86 ±.04）,（3.81 ±.04） mm vs （4.45 ±.04） mm;40 d：（4.56 ±.03）,（3.94 ±.05）,（3.74 ±.04）,（3.65 ±.02） mm vs （4.38 ±.03） mm] （P 〈 0.01）;the thickness of hind paw in tripterygium glycosides group and Mongolian medicine high dose group was significantly lower than that in Mongolian medicine low dose group （P 〈 0.01）.At 20,30 and 40 d time points,the arthritis indexes in tripterygium glycosides group,Mongolian medicine low,middle and high dose group were all significantly lower than those in model group [20 d：（8.2 ± 1.4）,（8.9 ± 1.1）,（8.3 ±1.3）,（8.8 ±1.7） scoresvs （10.9 ±1.3） scores,30d：（6.2 ±1.3）,（7.7±1.3）,（7.1 ±1.1）,（7.3±1.2） scores vs （9.7±1.2） scores,40d：（4.1 ±0.9）,（6.8±l.3）,（6.1 ±1.0）,（5.2±1.3） scores vs （8.9 ±0.7） scores] （P 〈0.05 or P 〈0.01）;the arthritis indexes in tripterygium glycosides group and Mongolian medicine high dose group were significantly lower than those in Mongolian medicine low dose group （P 〈0.01）.The level of IFN-γin serum in model group was significantly higher than that in normal group [（396 ±0） ng/L vs （238 ±36） ng/L];it was significantly decreased in tripterygium glycosides group,Mongolian medicine low,middle and high dose group [（251 ±6）,（323 ±1）,（295 ±4）,（258 ±3） ng/L vs （396 ±0） ng/L] （P 〈0.01）;no differences of IL-4 level were found among all groups （P 〉0.05）;the ratio of IFN-γ/IL-4 in model group was significantly higher than that in normal group [（28.5 ±.2） vs （19.4 ±.2）];it was significantly decreased in tripterygium glycosides group,Mongolian medicine middle and high dose group [（21.1±.3）,（22.1±.0）,（21.4±.6） vs （28.5 ±.2）] （P〈0.01）.The expressions ofIFN-γ and IL-4 in model group were significantly higher than those in normal group [（8.4 ±2.3） scores vs （2.1 ±.8） scores,（7.5 ±1.2） scores vs （1.8 ±0.7） scores];in tripterygium glycosides group,Mongolian medicine middle and high dose group,the expression of IFN-γ was significantly lower than that in model group [（3.6 ±.1）,（5.4 ±2.3）,（3.7 ±2.1） scores vs （8.4 ±2.3） scores];in tripterygium glycosides group and Mongolian medicine high dose group,the expression of IL-4 was significantly lower than that in model group [（2.1 ±0.9）,（3.8 ±1.4） scores vs （7.5 ±1.2） scores] （P 〈 0.01）.Conclusion Mongolian medicine Senden decoction can improve the general conditions and symptoms of arthritis in CIA rats and reduce the the expressions of IFN-γ and IL-4,with similar effect at high dose compared with tripterygium glycosides.
出处
《中国医药》
2015年第10期1485-1489,共5页
China Medicine
基金
国家自然科学基金（81360574）
关键词
胶原诱导性关节炎
蒙药森登
干扰素Γ
白细胞介素4
Collagen induced arthritis
Mongolian medicine Senden Decoction
Interferon γ
Interleukin 4
