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目的:探讨金铁锁(PR)及其总皂苷(PRTS)的抗炎镇痛作用,并探讨其抗炎机制。方法:实验动物随机分为空白组(大鼠)、模型组(大鼠、小鼠)、阳性药组(小鼠:吲哚美辛,元胡止痛胶囊0.585 g·kg~(-1)),金铁锁提取物(PR)高、中、低剂量组(小鼠:0.651 1,0.217,0.072 35 g·kg~(-1),大鼠:0.450 8,0.150 3,0.050 08 g·kg~(-1)),金铁锁总皂苷(PRTS)高、低剂量组(小鼠:0.233 4,0.025 94 g·kg~(-1),大鼠:0.161 6,0.017 96 g·kg~(-1))。采用醋酸诱导扭体实验和热板实验来评价镇痛作用;采用二甲苯诱导小鼠耳肿胀实验,脂多糖(LPS)诱导大鼠腹膜炎来评价抗炎作用,通过苏木素-伊红(HE)染色观察大鼠腹膜组织的病理变化,酶联免疫吸附法(ELISA)测定血清中的炎症因子白细胞介素(IL)-6,IL-10。探寻潜在机制,通过大鼠肠系膜组织免疫组化观察肿瘤坏死因子(TNF)-α,IL-1β,核转录因子-κB(NF-κB)p65的表达。结果:与空白组比较,PR及PRTS各剂量组减轻小鼠耳肿胀(P<0.01),减少小鼠化学致痛扭体次数(P<0.01,P<0.05);PRTS高剂量组能提高小鼠痛阈值(P<0.01,P<0.05);与模型组比较,PR及PRTS各剂量组对急性腹膜炎大鼠腹膜组织病变有所改善,能降低炎症因子IL-6含量(P<0.01),同时降低TNF-α,IL-1β,NF-κB p65在肠系膜组织的表达,PR高剂量及PRTS高剂量组能降低IL-10含量(P<0.05)。结论:金铁锁及总皂苷具有一定的镇痛抗炎作用,其机制可能与下调炎症因子的释放与表达,抑制NF-κB信号通道有关。
Objective: To investigate the anti-inflammatory and analgesic effects of golden iron (PR) and its total saponins (PRTS) and to explore its anti-inflammatory mechanism. METHODS: Experimental animals were randomly divided into blank group (rats), model group (rats, mice), and positive drug group (mice: indomethacin, Yuanhu Zhitong capsule 0.585 g·kg -1) , Golden iron lock extract (PR) high, medium and low dose groups (mice: 0.651 1, 0.217, 0.072 35 g · kg -1, rats: 0.450 8, 0.150 3, 0.050 08 g · kg ~ ( -1)) High- and low-dose group of total saponins (PRTS) of Golden Retriever (mice: 0.233 4, 0.025 94 g·kg -1, rats: 0.161 6, 0.017 96 g·kg -1) ). Analgesic effect was evaluated by acetic acid-induced writhing and hot plate experiments; mouse ear swelling was induced by xylene, and peritonitis was induced by lipopolysaccharide (LPS) to evaluate anti-inflammatory effects by hematoxylin-eosin (HE) staining The pathological changes of rat peritoneal tissues were observed. The inflammatory cytokines interleukin (IL)-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). To explore potential mechanisms, the expression of tumor necrosis factor (TNF)-α, IL-1β, and nuclear factor-κB (NF-κB) p65 was observed through rat mesenteric tissue immunohistochemistry. Results:Compared with the blank group, the PR and PRTS dose groups reduced the ear swelling (P<0.01), reduced the number of chemically induced painful writhing (P<0.01, P<0.05). The PRTS high dose group was able to increase the small Rat pain threshold (P<0.01, P<0.05); Compared with the model group, PR and PRTS dose groups improved the peritoneal tissue lesions in rats with acute peritonitis, and could reduce the content of inflammatory factor IL-6 (P<0.01). At the same time, the expression of TNF-α, IL-1β, and NF-κB p65 were decreased in mesenteric tissue. High doses of PR and high doses of PRTS could reduce the content of IL-10 (P<0.05). Conclusion: Golden iron chain and total saponins have certain analgesic and anti-inflammatory effects. The mechanism may be related to down-regulation of the release and expression of inflammatory factors and inhibition of NF-κB signaling pathway.