雷公藤甲素诱导胶原导致的关节炎大鼠滑膜细胞凋亡的研究(英)

目的：以胶原诱导的关节炎(CIA)为动物模型，探讨雷公藤甲素能否诱导CIA大鼠滑膜细胞凋亡。 方法： 选用雄性Wistar大鼠造模，将造模成功的大鼠随机分为模型组和雷公藤甲素组。雷公藤甲素按40 μg/kg BW，肌注给药，每3 d 1次。凋亡检测：给药31 d后处死，取膝关节滑膜，作苏木素-伊红染色(HE)、电镜、缺口末端标记法(TUNEL)标记及流式细胞仪检测。 结果： 电镜下可见早期阶段的滑膜凋亡细胞。流式细胞仪检测结果显示：正常组、模型组、雷公藤甲素组的凋亡细胞分别为(0.87±0.24)%、(1.83±0.82)%和(3.98±1.16)%。正常组、模型组、雷公藤甲素组的S期细胞分别为(3.4±0.7)%、(8.0±1.4)%和(3.3±1.2)%。雷公藤甲素组与模型组比较差异均显著(P＜0.01)。TUNEL标记结果显示：正常组、模型组、雷公藤甲素组的凋亡细胞分别为(1.0±0.4)%、(2.2±1.0)%和(4.5±0.9)%，雷公藤甲素组与模型组的差异显著(P＜0.01)。 结论： 本实验首次阐明了雷公藤甲素可诱导CIA大鼠滑膜细胞的凋亡。

Triptolide induces apoptosis of rat synoviocytes in collagen-induced arthritis

AIM: To determine whether triptolide induce apoptosis of synovial cells in collagen - induced arthritis(CIA) in rats. METHODS: The male Wistar rats were used to make CIA models by immunized with Bovine collagen Ⅱ ( BC Ⅱ )in Freund's complete adjuvant (FCA). A total of 20 CIA rats were randomly divided into 2 groups, triptolide group (10 rats) and CIA control group (10 rats). Triptolide group were administered with triptolide at 40 μg/kg body weight intramuscularly every three days. CIA control group andanother 10 age - matched normal rats were given normal saline instead. The rats were sacrificed on the 31st day after the triptolide administration. The pieces of synovium of the rat knee joints were harvested. The synovium was examined by HE staining and electron microscope. The apoptosis was tested by TUNEL and flow cytometer. RESULTS: The earlier phase of apoptotic synoviocytes were observed under the electron microscope. The flow cytometry showed that the percentage of the apoptotic cells was (3.98 ± 1.16)% in the triptolide group, (1.83 ± 0.82)% in the CIA control group, and (0.87 ±0.24)% in the normal group (P＜0.01: triptolide vs control group). While the percentage of the cells in DNA synthesis phase was (3.3± 1.2)% in the triptolide goup, (8.0± 1.4)% in the CIA control group, and (3.4 ± 0.7)% in the normal group.There is significantly different in the apoptosis changes between the triptolide group and the CIA control group ( P ＜ 0.01: triptolide vs CIA control group). The TUNEL labeling demonstrated that the percentage of the apoptotic cells was (4.5 ± 1.0)% in the triptolide group, (2.2 ± 1.0) % in the CIA control group, and ( 1.0 ± 0.4) % in the normal group. The difference of apoptotic rate between the triptolide group and the CIA control group is significant ( P ＜ 0.01). CONCLUSION: This study demonstrates that triptolide can induce apoptosis in CIA rats, which may be one of the mechanisms that triptolide treats the rheumatoid arthritis.