Tangshan Clinic Medicine College of Hebei Medical University, Tangshan, Hebei, 063000, China.
Tangshan Clinic Medicine College of Hebei Medical University, Tangshan, Hebei, 063000, China.
Asian Pac J Trop Med. 2014 Dec;7(12):996-9. doi: 10.1016/S1995-7645(14)60175-9.
To investigate the therapeutic effect of the intervention treatment with different doses of Captopril on TNF-αcontents in serum of rheumatoid arthritis (RA) rats, and to provide the theoretical proofs for clinical application of Captopril in treatments of rheumatoid diseases.
Fifty Wistar rats were randomly divided into 5 groups, namely, Group A, Group B, Group C, Group D, Group E with 10 rats in each group. Injection of Freund's complete adjuvant was employed to establish adjuvant-induced arthritis model in rats. Group A was model group; after model establishment, rats were treated with 20 mL normal saline as placebo (ip.). Rats in Group B were treated with 8 mg/kg cyclophosphamide (ip.). Rats in Group C, D and E were intraperitoneally injected with 30 mg/kg, 100 mg/kg and 300 mg/kg Captopril respectively. Rats in each group were subjected to continuous treatment for 3 weeks, and then sacrificed. Eyeballs of rats were excised and blood was collected. TNF-αcontent in serum were detected using ELISA; each group rats were compared for the hind legs arthrocele. Right ankle tissues of rats were collected to prepare section, and microscopic observation of pathological changes was performed.
TNF-αcontent in serum of Group A rats was significantly higher than that of rats in other 4 groups (P<0.05). TNF-αcontent in serum of Group B rats was significantly lower compared with that of rats in Groups C, D and E. The highest TNF-αcontent in serum of rats treated with Captopril was found in Group C, followed by Groups D and E (P<0.05). Right ankle arthrocele of rats in Groups B, C, D and E in early stage showed no statistical difference compared with that of Group A rats (P>0.05). From Day 8, ankle arthrocele of rats in Groups B, C, D and E was obviously relieved compared with that of Group A rats; the anti-inflammatory effects were gradually enhanced with the extension of medication time. Treatments of Groups C, D and E showed significant activities against tardive arthrocele; the degree of ankle arthrocele in rats of these three groups was lower than that of Group A rats (P<0.01). Histological observation showed that large amount of inflammatory cells and plasmocyte infiltration was found in ankle synovial tissues of Group A rats. Relief of hyperaemia and edema of right ankle synovial tissues as well as significant decrease in synoviocyte layer hyperplasia, intra-articular inflammatory cells infiltration and cartilago articularis damage degree etc. were observed in Groups B, C, D and E.
Intervention treatment with Captopril can effectively reduce the TNF-αcontent in serum of rheumatoid arthritis rats and inhibit the generation of inflammatory factors, so as to achieve the therapeutic effect.
研究卡托普利不同剂量干预治疗对类风湿关节炎(RA)大鼠血清肿瘤坏死因子-α(TNF-α)含量的影响,为卡托普利临床应用于治疗类风湿疾病提供理论依据。
50 只 Wistar 大鼠随机分为 5 组,每组 10 只,分别为 A 组、B 组、C 组、D 组、E 组。采用弗氏完全佐剂建立大鼠佐剂性关节炎模型。A 组为模型组;造模成功后,A 组给予 20 mL 生理盐水作为安慰剂(ip.)。B 组给予环磷酰胺 8 mg/kg(ip.)。C、D、E 组分别腹腔注射 30 mg/kg、100 mg/kg、300 mg/kg 卡托普利。各组大鼠连续治疗 3 周后处死,取眼球采血,采用 ELISA 法检测血清 TNF-α含量;各组大鼠比较后肢踝关节肿胀度。取大鼠右侧踝关节组织制成切片,进行病理变化的显微镜观察。
A 组大鼠血清 TNF-α含量明显高于其他 4 组(P<0.05)。B 组大鼠血清 TNF-α含量明显低于 C、D、E 组。C 组大鼠血清 TNF-α含量最高,其次为 D 组和 E 组(P<0.05)。B、C、D、E 组大鼠早期右侧踝关节肿胀与 A 组大鼠比较无统计学差异(P>0.05)。从第 8 天开始,B、C、D、E 组大鼠踝关节肿胀明显缓解,与 A 组大鼠比较差异有统计学意义(P<0.05);随着用药时间的延长,抗炎作用逐渐增强。C、D、E 组治疗后迟发性关节炎活动度明显,三组大鼠踝关节肿胀程度低于 A 组大鼠(P<0.01)。组织学观察发现,A 组大鼠踝关节滑膜组织大量炎性细胞和浆细胞浸润。B、C、D、E 组大鼠右踝关节滑膜组织充血水肿缓解,滑膜细胞层增生、关节腔内炎性细胞浸润、软骨关节损伤程度等明显减轻。
卡托普利干预治疗可有效降低类风湿关节炎大鼠血清 TNF-α含量,抑制炎症因子的产生,从而达到治疗效果。