目的 探討姜黃素通過核因子-κB（NF-κB）信號(hào)通路對(duì)高糖高脂飲食誘導(dǎo)的糖尿病模型大鼠胰島細(xì)胞形態(tài)和功能的影響。方法 采用高糖高脂飼料＋ip鏈脲佐菌素法制備糖尿病大鼠模型，將模型成功 SD大鼠隨機(jī)分為5組：模型組、二甲雙胍（200 mg·kg^-1，陽性藥）組和姜黃素低、中、高劑量（50、150、250 mg·kg^-1）組，對(duì)照組不造模。ig給藥，每天1次，連續(xù)6周，對(duì)照組同時(shí)注射等量無菌磷酸鹽緩沖液（PBS）。觀察SD大鼠體質(zhì)量變化；血糖儀檢測(cè)空腹血糖；ELISA法檢測(cè)血清C肽水平；生化分析儀檢測(cè)血清中糖化血紅蛋白、三酰甘油（TG）、總膽固醇（TC）、低密度脂蛋白膽固醇（LDL-C）、高密度脂蛋白膽固醇（HDL-C）、丙氨酸氨基轉(zhuǎn)移酶（ALT）、天冬氨酸氨基轉(zhuǎn)移酶（AST）、總膽紅素（TBil）、血肌酐（Scr）、血尿素氮（BUN）、尿酸（UA）水平；取胰腺進(jìn)行 HE 染色，于光鏡下觀察胰島形態(tài)學(xué)改變；免疫組化染色法觀察胰島 NF-κB 的陽性表達(dá)；Western blotting法檢測(cè)NF-κB信號(hào)通路相關(guān)蛋白表達(dá)；提取胰島細(xì)胞，免疫熒光染色觀察胰島素分泌，葡萄糖刺激的胰島素分泌（GSIS）實(shí)驗(yàn)檢測(cè)胰島素分泌量。結(jié)果 與模型組比較，各給藥組體質(zhì)量在治療第2周時(shí)開始緩慢增長(zhǎng)，第3、4周體質(zhì)量顯著升高（P＜0.05）；血糖水平顯著降低（P＜0.05），血清 C 肽水平顯著升高（P＜0.05）；糖化血紅蛋白、TG、TC、LDL-C、ALT、AST、Scr、BUN、UA水平顯著降低（P＜0.05），HDL-C水平顯著升高（P＜0.05）；胰島大小和形態(tài)逐漸恢復(fù)正常，胰島細(xì)胞依次變得更清晰完整，導(dǎo)管系統(tǒng)內(nèi)的囊性擴(kuò)張也逐漸減少；NF-κB陽性細(xì)胞減少；p-P65蛋白表達(dá)顯著降低（P＜0.05），p-IκBα蛋白表達(dá)顯著升高（P＜0.05）；胰島原代細(xì)胞分泌胰島素顯著增加（P＜0.05）。結(jié)論 姜黃素可以保護(hù)糖尿病大鼠胰島細(xì)胞正常形態(tài)，維持胰島細(xì)胞功能，減輕糖尿病大鼠癥狀，其機(jī)制可能與調(diào)控NF-κB信號(hào)通路有關(guān)。

Objective To investigate the effect of curcumin through NF-κB signaling pathway on the morphology and function of islet cells in diabetes mellitus rats induced by high glucose and high-fat diet. Methods The diabetes rat model was prepared by the method of high sugar and high fat diet + ip streptozotocin. The successfully modeled SD rats were randomly divided into five groups: the model group, metformin (200 mg·kg^-1, positive drug) group, and low, medium, and high dose curcumin (50, 150, 250 mg·kg^-1) groups. The control group was not modeled. The control group was injected with an equal amount of sterile phosphate buffer (PBS) once a day for six weeks. Observe the changes in body mass of SD rats; The fasting blood glucose was measured by a blood glucose meter. Serum C-peptide level was detected by ELISA. The serum levels of glycosylated hemoglobin, triacylglycerol (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), serum creatinine (Scr), blood urea nitrogen (BUN), and uric acid (UA) were measured by a biochemical analyzer. The pancreas was taken for HE staining, and the morphological changes of the islets were observed under light microscopy. Observation of islet positive expression of NF-κB by immunohistochemical staining. Detection of NF-κB signal pathway related proteins expression by Western blotting.Extract islet cells, observe insulin secretion by immunofluorescence staining, and detect insulin secretion by glucose stimulated insulin secretion (GSIS) experiment. Results Compared with the model group, the body mass of each treatment group began to slowly increase at the second week of treatment, and significantly increased at the third and fourth weeks (P＜0.05). The level of blood glucose significantly decreased (P＜0.05), while the level of serum C-peptide significantly increased (P＜0.05). The levels of glycosylated hemoglobin, TG, TC, LDL-C, ALT, AST, Scr, BUN, and UA decreased significantly (P＜0.05), while the levels of HDL-C increased significantly (P＜0.05). The size and morphology of the islets gradually returned to normal, the islet cells gradually became clearer and complete, and the cystic expansion in the ductal system gradually decreased. NF-κB positive cells decreased. The expression of p-P65 protein was significantly decreased (P＜0.05) and the protein expression of p-IκBα was significantly increased (P＜0.05). Insulin secretion by primary islet cells was significantly increased (P＜0.05). Conclusion Curcumin can protect the normal morphology of islet cells in diabetic rats, maintain the function of islet cells, and alleviate the clinical symptoms of diabetic rats. The mechanism may be related to the regulation of NF-κ B signaling pathway.

延安市科學(xué)技術(shù)局資助項(xiàng)目（2018CGZH-15）