摘要
目的 探讨藏红花素对痔疮模型大鼠肛周病理组织形态及炎症反应的影响以及核转录因子E2相关因子2(Nrf2)/血红素加氧-1(HO-1)通路发挥的作用。方法 采用醋酸贴敷法构建大鼠急性痔疮模型;将造模成功大鼠分为模型组、阳性组和低、中、高剂量(L、M、H)藏红花素组、藏红花素+ML385(Nrf2抑制剂)组,每组10只,并取10只大鼠设为对照组;给药1周后,肛周组织病变评分;ELISA检测血清中炎症因子水平;血常规检测血液中白细胞、淋巴细胞、中性粒细胞水平;HE染色检测肛周病理组织形态变化;Western blot检测肛周组织中Nrf2、HO-1蛋白水平。结果 与对照组比较,模型组大鼠肛周黏膜上皮坏死、有出血、炎性细胞浸润,肛周组织病变评分、血清中IL-1β、TNF-α、IL-6水平,血液中白细胞、淋巴细胞、中性粒细胞数显著升高,肛周组织Nrf2、HO-1蛋白水平显著降低(P<0.05);与模型组比较,阳性组肛周组织病变评分、血清中IL-1β、TNF-α、IL-6水平、藏红花素-L、M、H组大鼠肛周组织损伤明显改善,腺体整齐排列、炎性浸润减轻、出血减轻,肛周组织病变评分、血清IL-1β、TNF-α、IL-6水平,血液白细胞、淋巴细胞、中性粒细胞数显著降低,肛周组织Nrf2、HO-1蛋白水平显著升高,呈剂量依赖性(P<0.05);与藏红花素-H组比较,藏红花素+ML385组大鼠肛周组织严重受损,炎性细胞浸润,肛周组织病变评分[(5.12±0.62)分]、血清中IL-1β[(121.65±9.32)pg/mL]、TNF-α[(184.65±10.65)ng/L]、IL-6[(129.36±10.67)pg/mL]水平升高,血液白细胞、淋巴细胞、中性粒细胞数也显著升高,肛周组织Nrf2、HO-1蛋白水平显著降低(P<0.05)。结论 藏红花素可通过激活Nrf2/HO-1通路有效缓解急性痔疮大鼠肛周病理组织形态,降低炎症反应。
Objective To investigate the impacts of crocin on the morphology and inflammatory response of perianal pathological tissue in hemorrhoid model rats,and the role of nuclear factor erythroid⁃derived 2⁃related factor 2(Nrf2)/heme oxygenase⁃1(HO⁃1)pathway.Methods A rat model of acute hemorrhoids was established using acetic acid application method;the successfully modeled rats were divided into model group,positive group,crocin⁃L group,crocin⁃M group,crocin⁃H group,crocin+ML385(Nrf2 inhibitor)group,with 10 rats in each group,and 10 rats were set as the control group;after one week of administration,the perianal tissue lesion score was evaluated;ELISA was applied to detect the levels of inflammatory factors in the serum of rats in each group;blood routine tests were applied to detect the levels of white blood cells,lymphocytes,and neutrophils in the blood of rats in each group;HE staining was applied to detect morphological changes in the perianal pathological tissues of rats in each group;Western blot was applied to detect the levels of Nrf2 and HO⁃1 proteins in the perianal tissues of rats in each group.Results Compared with the control group rats in model group had necrosis,bleeding,inflammatory cell infiltration of the perianal mucosal epithelium,the score of perianal tissue lesions,levels of IL⁃1β,TNF⁃α,and IL⁃6 in serum,and the numbers of white blood cells,lymphocytes,and neutrophils in the blood were obviously increased,the levels of Nrf2 and HO⁃1 proteins in perianal tissue were obviously reduced(P<0.05);Compared with the model group,the perianal tissue damage in the positive group score,crocin⁃L,M,and H groups obviously improved,with orderly arrangement of glands,reduced inflammatory infiltration,and reduced bleeding,the score of perianal tissue lesions,levels of IL⁃1β,TNF⁃α,and IL⁃6 in serum,and the numbers of white blood cells,lymphocytes,and neutrophils in the blood were obviously reduced,the levels of Nrf2 and HO⁃1 proteins in perianal tissue were obviously increased,in a dose⁃dependent manner(P<0.05);compared with the crocin⁃H group,the perianal tissue of rats in crocin+ML385 group was severely damaged,with inflammatory cell infiltration,the score of perianal tissue lesions[(5.12±0.62)score],the levels of IL⁃1β[(121.65±9.32)pg/mL],TNF⁃α[(184.65±10.65)ng/L],and IL⁃6[(129.36±10.67)pg/mL]in serum,and the numbers of white blood cells,lymphocytes,and neutrophils in the blood were obviously increased,the levels of Nrf2 and HO⁃1 proteins in perianal tissue were obviously reduced(P<0.05).Conclusion Crocin can effectively alleviate perianal pathological tissue morphology and reduce inflammatory response in rats with acute hemorrhoids by activating the Nrf2/HO⁃1 pathway.
作者
张晓婷
刘晓军
席锋祥
司华清
ZHANG Xiao-ting;LIU Xiao-jun;XI Feng-xiang;SI Hua-qing(Department of Proctology,Zhangjiakou Fifth Hospital,Heibei,Shijiazhuang Province 075000,China)
出处
《解剖学研究》
CAS
2023年第6期562-567,共6页
Anatomy Research
基金
张家口市重点研发计划项目(2121121D)。
