[关键词]
[摘要]
目的 研究散结镇痛胶囊(SJZT)对大鼠慢性盆腔炎模型的抗炎、抗纤维化作用及相关机制。方法 取60只成年未孕雌性大鼠,随机选取10只进行假手术,其余50只大鼠采用子宫内注射苯酚胶浆法复制大鼠慢性盆腔炎模型,术后正常喂养。第14天,根据体质量将其随机分为模型组、地塞米松(DEX)组及SJZT低、中、高剂量(0.192、0.384、0.768 g/kg)组,ig给药,假手术组、模型组大鼠ig 0.5% CMC-Na溶液,每天1次,连续30 d。末次给药后,大鼠取血、子宫组织,HE和Masson染色观察子宫病理形态改变,ELISA法检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、基质血小板衍化生长因子(PDGF)、金属蛋白酶抑制因子(TIMP)水平,Western blotting法检测子宫组织中磷酸化细胞外调节蛋白激酶(p-Erk1/2)、核转录因子-κB p65(NF-kB p65)、p-JNK、基质金属蛋白酶-2(MMP-2)、MMP-9蛋白表达水平。结果 与模型组比较,SJZT能显著改善慢性盆腔炎大鼠子宫腔壁结构,减轻表面上皮细胞变性坏死、炎细胞浸润及固有层充血,减轻子宫固有层胶原纤维增生程度;显著降低血清中TNF-α、IL-1β、PDGF、TIMP水平。同时SJZT能抑制大鼠子宫p-ERK1/2、p-JNK、NF-κB p65蛋白表达,促进MMP-2、MMP-9蛋白表达。结论 SJZT能够有效改善苯酚胶浆致大鼠慢性盆腔炎模型的炎症反应及组织纤维化,其作用机制可能与调控NF-κB及MAPK信号通路相关,抑制体内炎症反应,同时使细胞外基质合成减少与分解增加,促进纤维化修复。
[Key word]
[Abstract]
Objective The anti-inflammatory and anti-fibrotic effects of Sanjie Zhentong Capsule (SJZT) on chronic pelvic inflammation in rats were investigated and its underlying mechanisms were explored. Methods Ten rats regarded as normal group with sham operation were randomly selected from 60 female SD rats, and the remaining rats were injected with phenol mucilage in the left uteri to replicate chronic pelvic inflammatory disease. On day 14, after the operation, according to body weight, the 50 rats were randomly allocated to model group, dexamethasone (DEX) group, SJZT low dose group (0.192 g/kg), SJZT middle dose group (0.384 g/kg), and SJZT high dose group (0.768 g/kg). The drugs were dissolved in 0.5% CMC-Na solution and administered respectively, while 0.5% CMC-Na solution was given to the normal and model group. After all the animals were treated by oral gavage once a day for 30 d, the blood and the left uteri were collected. The uterine tissues were fixed and stained with haematoxylin-eosin (HE) and Masson's trichrome for histopathology examination and the concentrations of TNF-α, IL-1β, PDGF, and TIMP in serum were assayed by ELISA. The protein expression levels of p-ERK1/2, p-JNK, NF-κB p65, MMP-2, and MMP-9 in the uteri were also detected by Western blotting. Results Compared with the model group, SJZT could effectively improve the arrangement disorder of cavity wall, reduce the degeneration and necrosis of epithelial cells, the infiltration of inflammatory cells and the congestion of lamina propria, and alleviate the proliferation of collagen fibers in lamina propria. SJZT could also reduce the concentrations of TNF-α, IL-1β, PDGF, and TIMP in serum. Moreover, the protein expression of p-ERK1/2, p-JNK, and NF-κB p65 in the uteri were inhibited significantly, and at the same time the protein expression of MMP-2 and MMP-9 was increased markedly by SJZT. Conclusion SJZT exhibits robust anti-inflammatory and anti-fibrosis effects in chronic pelvic inflammatory disease model induced by phenol mucilage. Its mechanisms may be related to regulating NF-κB and MAPK signaling pathways, inhibiting inflammation, reducing the synthesis of extracellular matrix (ECM), increasing the degradation of ECM and promoting the repair of fibrosis.
[中图分类号]
[基金项目]
科技部重大新药创制:现代中药创新集群与数字制药科技平台(2013ZX09402203)