目的 探究沙棘多糖(seabucthorn polysaccharide,SP)对糖尿病大鼠胰岛素抵抗和肝、肾功能损伤的影响。 方法 将大鼠随机分为对照组、链脲佐菌素(streptozocin,STZ)组、盐酸罗格列酮(rosiglitazone,RSG)组(4 mg·kg-1·d-1)和SP低、中、高剂量组(50、100、200 mg·kg-1·d-1),除对照组外其余大鼠均建立为Ⅱ型糖尿病模型。药物处理后,通过天平、血糖仪、Elis检测大鼠体重、双侧肾重、空腹血糖和胰岛素水平,计算肾肥大指数、胰岛素抵抗指数;Elisa检测HbA1C、脂联素;生化分析仪检测TG、TC、LDL-C、HDL-C、PRO、Scr、BUN水平;油红O染色、HE染色观察肝脂肪沉积情况和肾组织形态;Western Blot检测PERK/ATF4/CHOP通路活化水平。 结果 与STZ组相比,SP中、高剂量组大鼠体重、脂联素、HDL-C升高(P<0.05),血糖、胰岛素抵抗指数、肾肥大指数、HbA1C、血浆胰岛素、TG、TC、LDL-C、PRO、Scr、BUN水平下调(P<0.05),缓解大鼠肝脂质沉积和肾损伤,且抑制PERK/ATF4/CHOP通路活性。 结论 沙棘多糖可缓解糖尿病大鼠胰岛素抵抗和肝、肾功能损伤,其机制可能与抑制PERK/ATF4/CHOP通路活性有关。
Objective To investigate the effects of seabuckthorn polysaccharide (SP) on insulin resistance, liver and kidney function damage in diabetic rats. Methods Rats were randomly divided into the following groups: a control group, a streptozocin (STZ) group, a rosiglitazone (RSG) group (4 mg.kg-1.d-1) and a low, a medium and a high dose SP group (50, 100, 200 mg.kg-1.d-1). All rats except the control group were established as type II diabetes model. After drug treatment, the body weight, bilateral kidney weight, fasting blood sugar and insulin levels were measured by balance, blood glucose meter and Elisa, and renal hypertrophy index and insulin resistance index were calculated. The levels of HbA1C and adiponectin were detected by Elisa, and the levels of TG, TC, LDL-C, HDL-C, PRO, Scr and BUN were detected by biochemical analyzer. Oil red O and HE staining were used to observe hepatic fat deposition and renal histomorphology. Western Blot was used to detect the activation level of PERK/ATF4/CHOP pathway. Results Compared with the model group, the body weight, adiponectin and HDL-C content in the medium and high doses of SP group significantly increased (P<0.05). While the blood glucose content, insulin resistance index, kidney hypertrophy index, HbA1C, plasma insulin, the levels of TG, TC, LDL-C, proteinuria, Scr, BUN in the medium and high doses of SP group significantly down-regulated (P<0.05). SP could alleviate liver lipid deposition and kidney damage, and inhibit the activity of PERK/ATF4/CHOP pathway in rats. Conclusions Seabucthorn Polysaccharide can alleviate insulin resistance, liver and kidney function damage in diabetic rats, its mechanism may be related to the inhibition of PERK/ATF4/CHOP pathway activity.
[1] Lehtonen HM, Järvinen R, Linderborg K, et al. Postprandial hyperglycemia and insulin response are affected by sea buckthorn (Hippophaë rhamnoides ssp. Turkestanica) berry and its ethanol-soluble metabolites[J]. Eur J Clin Nutr, 2010, 64(12): 1465-1471. DOI: 10.1038/ejcn.2010.173.
[2] 宋春梅,杜鹃,葛红娟. 沙棘果对高脂饲料大鼠血脂和肝脏的保护作用[J]. 卫生研究, 2015, 44(4): 628-631. DOI: 10.19813/j.cnki.weishengyanjiu.2015.04.023
[3] Quentin T, Steinmetz M, Poppe A, et al. Metformin differentially activates ER stress signaling pathways without inducing apoptosis[J]. Dis Model Mech, 2012, 5(2): 259-269. DOI: 10.1242/dmm.008110.
[4] 郭凤霞, 曾阳,李锦萍,等. 沙棘多糖对α-葡萄糖苷酶活性及正常小鼠血糖的影响 [J]. 药学学报, 2013, 48(4): 604-608. DOI: 10.16438/j.0513-4870.2013.04.012
[5] Kwon EY, Lee J, Kim YJ, et al. Seabuckthorn leaves extract and flavonoid glycosides extract from seabuckthorn leaves ameliorates adiposity, hepatic steatosis, insulin resistance, and inflammation in diet-induced obesity[J]. Nutrients, 2017, 9(6): 596. DOI: 10.3390/nu9060569.
[6] Amiri Dash Atan N, Koushki M, Motedayen M, et al. Type 2 diabetes mellitus and non-alcoholic fatty liver disease: a systematic review and meta-analysis[J]. Gastroenterol Hepatol Bed Bench, 2017, 10 (Suppl1): S1-S7.
[7] Aghadavod E, Khodadadi S, Baradaran A, et al. Role of oxidative stress and inflammatory factors in diabetic kidney disease[J]. Iran J Kidney Dis, 2016, 10(6): 337-343.
[8] Kawanami D, Matoba K, Utsunomiya K. Signaling pathways in diabetic nephropathy[J]. Histol Histopathol, 2016, 31(10): 1059-1067. DOI: 10.14670/HH-11-777.
[9] Kanwar YS, Wada J, Sun L, et al. Diabetic nephropathy: mechanisms of renal disease progression[J]. Exp Biol Med (Maywood), 2008, 233(1): 4-11. DOI: 10.3181/0705-MR-134.
[10] Hu SJ, Shu B, Jin H, et al. Therapeutic role of tangshenkang granule in rat model with diabetic nephropathy[J]. Chin J Integr Med, 2018, 24(8): 600-605. DOI: 10.1007/s11655-016-2607-x.
[11] Cao J, Dai DL, Yao L, et al. Saturated fatty acid induction of endoplasmic reticulum stress and apoptosis in human liver cells via the PERK/ATF4/CHOP signaling pathway[J]. Mol Cell Biochem, 2012, 364(1-2): 115-129. DOI: 10.1007/s11010-011-1211-9.