大黄丹参对高脂饮食诱发的胰腺纤维化大鼠影响的研究

目的:研究大黄丹参对高脂饮食诱导的胰腺纤维化大鼠氧化应激、内质网应激相关因子的影响。方法:将40只雄性清洁级SD大鼠，采用随机数表法均分成对照组、模型组、大黄丹参低、中、高剂量组，每组8只；对照组喂以普通饲料，其余4组均喂以高脂饲料连续10周建立胰腺纤维化模型。造模同时，各组以相应药物灌胃，对照组与模型组生理盐水灌胃，...

Effect of rhubarb and salvia miltiorrhiza on pancreatic fibrosis induced by high fat diet in rats

Objective To study the effects of rhubarb and salvia miltiorrhiza on the pancreatic fibrosis in rats induced by high-fat whether via C-Jun N-terminal kinase(JNK),glucose responsive protein(GRP)and cysteinyl aspartate specific proteinase-12(Caspase-12)mRNA and protein regulation.Methods A total of 40 male specific pathogen free(SPF)SD rats were randomly divided into control group,model group,radix etrhizomarhei and salvia miltiorrhiza low,medium and high dose groups(n=8 each).The control group was fed on ordinary feed,and the animals in the rest of four groups were fed on high fat forage for 10 weeks to induce pancreatic fibrosis.At the same time,rhubarb and salvia miltiorrhiza low,medium and high dose groups were gavaged with the corresponding concentrations of drugs respectively.The control group and model group received oral saline.The pancreatic tissues were harvested and subjected to hematoxylin-eosin staining,and examined under the electron microscopy.Serum superoxide dismutase(SOD),glutathione(GSH),malondialdehyde(MDA),total cholesterol(TC)and triglyceride(TG)contents were determined by biochemical method.The expression of JNK,GRP,Caspase-12 mRNA and protein was detected by real time PCR and Western blotting respectively.One-way analysis of variance(ANOVA)was used for data comparison between groups.Results There were pathological changes such as swollen endoplasmic reticulum and narrowed intercellular space in the gross morphology and ultrastructure of pancreas in model group.Different doses of rhubarb and salvia miltiorrhiza could improve the gross morphological and ultrastructural changes of pancreas to varying degrees.The levels of SOD(24.71±2.35,33.80±3.21)and GSH(61.41±5.57,101.34±17.32)in rhubarb and salvia miltiorrhiza medium and high dose groups were higher than those in model group(12.77±3.17,32.05±5.59,P<0.01).The levels of MDA(7.10±0.61,6.13±0.63,5.47±0.57)and TG(0.43±0.08,0.38±0.06,0.22±0.03)in rhubarb and salvia miltiorrhiza low,medium and high dose groups were lower than those in model group(8.27±1.12,0.69±0.13,P<0.01).The TC levels in rhubarb and salvia miltiorrhiza medium and high dose groups(0.58±0.19,0.39±0.15)were lower than those in model group(1.18±0.44,P<0.05).JNK protein and mRNA expression in pancreatic tissue of rhubarb and salvia miltiorrhiza medium and high dose groups(0.74±0.09,0.69±0.10;0.33±0.04,0.25±0.02)was lower than the model group(0.99±0.12,1.00±0.00,P<0.05).The P-JNK protein expression in rhubarb and salvia miltiorrhiza medium and high dose groups(0.50±0.06,0.52±0.13)were lower than those in model group(1.13±0.11,P<0.01).The GRP protein and mRNA expression levels in pancreatic tissue of rhubarb and salvia miltiorrhiza middle and high dose groups were(0.67±0.13,0.38±0.14;0.51±0.02,0.26±0.02)were lower than in the model group(1.09±0.18,1.00±0.00,P<0.05).The Caspase-12 mRNA expression in pancreatic tissue of rhubarb and salvia miltiorrhiza middle and high dose groups(0.68±0.08,0.36±0.06)was lower than that of the model group(1.00±0.00,P<0.01).The Caspase-12 protein expression in the rhubarb and salvia miltiorrhiza high-dose group(0.41±0.10)was lower than that in the model group(0.95±0.13,P<0.01).Conclusion Rhubarb and salvia miltiorrhiza can inhibit pancreatic fibrosis by reducing oxidative stress and maintaining endoplasmic reticulum stress homeostasis.