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多糖治疗链脲佐菌素诱导糖尿病大鼠糖尿病肾病的作用及机制。

Effects and Mechanism of Polysaccharides in the Treatment of Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats.

机构信息

Basic Medical College, Jiamusi University, Jiamusi, Heilongjiang, China 154002.

School of Medicine, The First Affiliated Hospital of Jiamusi University, Jiamusi 154003, China.

出版信息

Biomed Res Int. 2022 Mar 8;2022:4314415. doi: 10.1155/2022/4314415. eCollection 2022.

DOI:10.1155/2022/4314415
PMID:35299891
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8923773/
Abstract

polysaccharides (GLP) have renal protection effect but there was no study on the diabetic nephropathy. This study was designed to investigate its effect and mechanism using a diabetic rat model induced by streptozotocin (50 mg/kg, i.p.). The diabetic rats were treated with GLP (300 mg/kg/day) for 10 weeks. The blood glucose, glycated hemoglobin, body weight, and the levels of blood creatinine, urea nitrogen, and urine protein were assessed. And renal pathologies were assessed by the tissue sections stained with hematoxylin-eosin, Masson's trichome, and periodic acid-Schiff. The expression of phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR), the autophagy proteins beclin-1, LC3-II, LC3-I, and P62; the apoptosis-related proteins caspase-3 and caspase-9; and the inflammation markers IL-6, IL-1, and TNF-ɑ were assessed. Results showed that GLP alleviated the impairment of renal function by reducing urinary protein excretion and the blood creatinine level and ameliorated diabetic nephropathy. The expression of p-PI3K, p-Akt, and p-mTOR in the diabetic kidney were significantly reduced in the GLP treatment group compared to the without treatment group. GLP treatment activated the autophagy indicators of beclin-1 and the ratio of LC3-II/LC3-I but reduced p62 and also inhibited the expression of caspase-3, caspase-9 and IL-6, IL-1, and TNF-ɑ. In conclusion, the effect of GLP amelioration diabetic nephropathy may be via the PI3k/Akt/mTOR signaling pathway by inhibition of the apoptosis and inflammation and activation of the autophagy process.

摘要

多糖(GLP)具有肾脏保护作用,但尚无关于糖尿病肾病的研究。本研究旨在通过链脲佐菌素(50mg/kg,腹腔注射)诱导的糖尿病大鼠模型来研究其作用和机制。糖尿病大鼠用 GLP(300mg/kg/天)治疗 10 周。评估血糖、糖化血红蛋白、体重以及血肌酐、尿素氮和尿蛋白水平。并通过苏木精-伊红、马松三色和过碘酸-Schiff 染色的组织切片评估肾脏病理。评估磷酸化磷脂酰肌醇 3 激酶(p-PI3K)、磷酸化蛋白激酶 B(p-Akt)和磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)、自噬蛋白 beclin-1、LC3-II、LC3-I 和 P62 的表达;凋亡相关蛋白 caspase-3 和 caspase-9;以及炎症标志物 IL-6、IL-1 和 TNF-ɑ。结果表明,GLP 通过减少尿蛋白排泄和血肌酐水平来减轻肾功能损害,并改善糖尿病肾病。与未治疗组相比,GLP 治疗组糖尿病肾脏中 p-PI3K、p-Akt 和 p-mTOR 的表达明显降低。GLP 治疗可激活自噬标志物 beclin-1 和 LC3-II/LC3-I 的比值,但降低 p62,并抑制 caspase-3、caspase-9 和 IL-6、IL-1 和 TNF-ɑ的表达。总之,GLP 改善糖尿病肾病的作用可能是通过抑制细胞凋亡和炎症以及激活自噬过程来抑制 PI3k/Akt/mTOR 信号通路。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75a4/8923773/11f2ccdf3d59/BMRI2022-4314415.001.jpg
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