Hp相关胃病病理演变及不同证候IL-1β蛋白差异表达特征

Differential Expression Characteristics of IL-1βin the Pathological Evolution of Gastric Mucosa and Chinese Medicine Syndromes in Helicobacter pylori-Related Gastric Diseases

目的通过对白细胞介素-1β(IL-1β)蛋白表达的定性定位分析,探索幽门螺杆菌相关胃病(HpGD)病理演变及不同证候的蛋白差异表达特征。方法收集548例HpGD受试者临床四诊资料,其中92例为常规体检受试者,456例为慢性非萎缩性胃炎、慢性萎缩性胃炎、胃溃疡或胃癌患者。所有受试者辨证分为无症状者、脾胃湿热、肝胃不和、脾气虚、瘀血内阻证5组。所有受试者在胃窦或胃黏膜病变处钳取标本,采用快速尿素酶和美蓝染色法检测Hp感染情况;HE染色观察胃黏膜病理组织学改变,分为相对正常、炎症、萎缩、癌前病变、重度异型增生、胃癌6组;Elivision plus标记法检测IL-1β蛋白并观察胃黏膜上皮表层、胃小凹、固有层腺体区的表达差异。结果与炎症组比较,Hp阴性者中IL-1β蛋白在胃癌及癌前病变组表达增高(P<0.05);与相对正常及炎症组比较,Hp阳性者IL-1β蛋白在癌前病变、重度异型增生及胃癌组表达增高(P<0.05),且重度异型增生组表达高于萎缩及癌前病变组(P<0.01)。不同证候间可见Hp阳性者中脾胃湿热证表达强度最高的趋势。胃黏膜上皮表层、胃小凹和固有层腺体区的IL-1β蛋白表达主要定位在胞浆,胞膜、胞核也见少量表达。随着胃黏膜从上皮表层、胃小凹到固有层腺体区,以及病理表现异型增生、肠化、癌变阶段,IL-1β蛋白胞浆表达强度不断增强(P<0.05)。结论IL-1β可能主要通过胞浆表达及Hp感染协同参与HpGD病理演变,且Hp感染、脾胃湿热证与IL-1β高表达或可为HpGD胃黏膜恶性病理演变提供早期预警信号。

Objective To investigate the differential expression characteristics of IL-1βin the pathological evolution of gastric mucosa and Chinese medicine syndromes in Helicobacter pylori-related gastric diseases(Hp GD)through qualitative and localization analyses.Methods The data from four diagnostic methods in Chinese medicine of 548 participants with Hp GD were collected.Of these,92 were routine physical examination participants,and 456 were patients with chronic non-atrophic gastritis,chronic atrophic gastritis,gastric ulcers,or gastric cancer.All participants were assigned to five groups according to syndrome typing,i.e,as non-symptomatic,Pi-Wei damp-heat syndrome,Gan-Wei disharmony syndrome,Pi-qi deficiency syndrome,and blockage of static blood syndrome.Biopsy specimens were obtained from the participants'gastric antrum and mucosal lesions.Hp infection was detected using rapid urease and methylene blue staining.The pathological changes of the gastric mucosa was observed using HE staining,and the participants were assigned to six groups,i.e,as healthy control,inflammation,gastric atrophy,precancerous gastric lesion,advanced precancerous lesion,and gastric cancer.IL-1βexpression was detected using the Elivision plus labeling,and expression differences were observed in the gastric mucosal epithelial surface,gastric pits,and glandular areas of the lamina propria.Results Among Hp-negative individuals,IL-1βprotein expression was higher in the gastric cancer and precancerous lesion groups than in the inflammation group(P<0.05).For Hp-positive individuals,IL-1βprotein expression was higher in the precancerous gastric lesions,advanced precancerous lesions,and gastric cancer groups compared with the inflammation and healthy control groups(P<0.05),with the advanced precancerous lesions group showing higher expression than the precancerous lesions and gastric cancer groups(P<0.01).There was a trend toward the highest expression intensity of Hp among Chinese medicine syndromes in those with Pi-Wei damp-heat syndrome.IL-1βprotein expression in the gastric mucosal epithelial surface,gastric pits,and glandular areas of the lamina propria was primarily localized in the cytoplasm,with minor expression in the cell membrane and nucleus.As the pathological condition progressed from epithelial surface,gastric pits,to glandular areas of the lamina propria,and through stages of dysplasia,intestinal metaplasia,and carcinoma,the cytoplasmic expression of IL-1βprotein intensified(P<0.05).Conclusions IL-1βmay primarily participate in the pathological evolution of Hp GD through cytoplasmic expression and synergistic interaction with Hp infection.This suggests that high IL-1βexpression,combined with Hp infection and Pi-Wei damp-heat syndrome,may provide early warning signals for the malignant transformation of gastric mucosa in Hp GD.