Zhong Ruihua, Ma Aying, Zhu Jianping, Li Guoting, Xie Shuwu, Li Zhao, Gui Youlun, Zhu Yan
Department of Reproductive Pharmacology, Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China.
School of Pharmacology, Guangdong Medical College, Dongguan 523808, China.
Evid Based Complement Alternat Med. 2016;2016:5649169. doi: 10.1155/2016/5649169. Epub 2016 Aug 11.
We evaluated the effectiveness of Kuntai Capsule (KTC) for treating endometriosis using rat model and investigated its preliminary mechanism of action involved. SD rats were implanted with endometrial tissues and treated with KTC for three weeks. Then, laparotomy was performed to examine volume changes of the autografts. The serum levels of TNF-α, IL-6, COX-2, E2, and P4 were measured through ELISA. TUNEL was performed to analyze the apoptosis on ectopic endometrium. Protein levels of caspases 8, 9, and 3 and cytochrome c in the ectopic and eutopic endometrium were measured by western blotting. Results showed that KTC significantly decreased the volumes of ectopic endometrium. The level of TNF-α increased and E2 decreased in the KTC treatment groups. TUNEL and western blot assay showed that KTC could induce apoptosis of endometriotic tissues, accompanied with the increased protein expression of caspases 8 and 9, activated caspase-3, and cytochrome c in a dose-dependent manner. However, these protein expression profiles were not affected in eutopic endometrium. Our findings suggest that KTC could inhibit the growth of ectopic endometrial tissue through upregulating the level of TNF-α and its downstream signaling, including caspases and cytochrome c.
我们使用大鼠模型评估了坤泰胶囊(KTC)治疗子宫内膜异位症的有效性,并研究了其初步作用机制。将子宫内膜组织植入SD大鼠体内,并用KTC治疗三周。然后,进行剖腹手术以检查自体移植组织的体积变化。通过酶联免疫吸附测定法(ELISA)检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、环氧化酶-2(COX-2)、雌二醇(E2)和孕酮(P4)的水平。采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)分析异位子宫内膜的细胞凋亡情况。通过蛋白质免疫印迹法检测异位和在位子宫内膜中半胱天冬酶8、9和3以及细胞色素c的蛋白水平。结果显示,KTC显著减小了异位子宫内膜的体积。KTC治疗组中TNF-α水平升高而E2水平降低。TUNEL和蛋白质免疫印迹分析表明,KTC可诱导子宫内膜异位组织的细胞凋亡,同时半胱天冬酶8和9的蛋白表达增加,半胱天冬酶-3激活,细胞色素c呈剂量依赖性增加。然而,在位子宫内膜中的这些蛋白表达情况未受影响。我们的研究结果表明,KTC可通过上调TNF-α及其下游信号(包括半胱天冬酶和细胞色素c)的水平来抑制异位子宫内膜组织的生长。