沙棘多糖抑制PERK/ATF4/CHOP通路缓解糖尿病大鼠胰岛素抵抗和肝肾功能损伤

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。

Seabuckthorn polysaccharide alleviates insulin resistance,liver and kidney function damage in diabetic rats by inhibiting PERK/ATF4/CHOP pathway

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.