D-半乳糖致小鼠胰腺损伤

目的探讨D-半乳糖(D-gal)对小鼠胰腺的损伤及其机制。方法 C57BL/6J小鼠随机分为对照组和D-gal组(D-gal 120 mg/kg,qd×42 d)。注射完成第2天,采外周血测定空腹血糖(FBG)与空腹胰岛素(FINS)水平;称小鼠体质量(g)与胰腺湿重(mg)计算胰腺脏器指数;HE染色观察胰腺组织形态学;透射电镜观察胰腺细胞超微结构;制备冷冻切片,衰老相关β-半乳糖苷酶(SA-β-gal)染色检测胰岛内染色阳性细胞的相对吸光度(RA)值;免疫组织化学法观察胰腺组织晚期糖基化终产物(AGEs)的RA值;制备胰腺组织匀浆检测超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)和丙二醛(MDA)含量。结果 D-gal组小鼠FBG显著升高(P0.05),FINS水平降低;胰腺湿重和胰腺脏器指数明显升高(P0.01);胰腺光镜结构无显著损伤,但胰岛内单个有核细胞所占面积增加(P0.05);胰腺内外分泌部显示细胞超微结构损伤,脂褐素明显沉积;胰腺SA-β-gal染色阳性细胞的RA值增加(P0.05);AGEs阳性表达区域RA值升高(P0.01);SOD与T-AOC含量降低(P0.05),MDA含量升高(P0.01)。结论 D-gal复制衰老小鼠模型可致胰腺损伤,发生机制可能与D-gal致胰腺细胞氧化应激损伤有关。

Murine pancreatic injury induced by D-galactose

Objective To explore the effect of D-galactose(D-gal) on murine pancreatic injury and its pathogenesis.Methods C57BL/6J mice were randomly divided into control group and D-gal model group D-gal 120 mg/(kg · d) for 42 days].On the 2nd day after drug injection completed,the peripheral blood was taken for measuring the level of fasting blood glucose(FBG) and fasting insulin(FINS);and then the organ index of pancreas was calculated by the ratio of pancreatic wet weight(mg) and mouse body weight(g);HE stain was routinely prepared to observe the histologic structure of pancreatic tissue;the TEM was used to analyze ultrastructural changes of pancreatic cells;the pancreatic frozen sections were prepared to test senescence-associated β-galactosidase (SA-β-gal) and its relative absorbance(RA) of positively stained cells in the pancreatic islets;immunohistochemistry assays to study advanced glycation end products (AGEs) and its RA;pancreas tissue homogenate was made to detect the content of superoxide dismutase(SOD),malonaldehyde(MDA) and total antioxidant capacity(T-AOC).Results In D-gal group mice,the FBG increased(P＜0.05) and FINS reduced;pancreas wet weight and organ increased obviously (P＜0.01);light microscopic structure of the pancreas presented without typical pathologic change,however the single nucleated cell's area within the islet was increased significantly(P＜0.05);the pancreas endocrine and exocrine cells were showed the ultrastructure damaged and lipofuscin formation increased;the RA of positive pancreas cells in SA-β-gal staining increased(P＜0.05);the RA of AGEs positive regional expression markedly increased (P＜0.01);the content of SOD and T-AOC decreased (P ＜ 0.05),the content of MDA increased (P ＜ 0.01).Conclusions Aging mice model replicated by D-gal can cause the pancreatic injury,its mechanisms may be closely related to oxidative injury of pancreatic cells caused by D-gal.