Tong Fei, Tang Xiangyuan, Luo Lei, Li Xin, Xia Wenquan, Lu Chao, Liu Daojun
Department of Pharmaceutical Chemistry, Medical College, Shantou University, 22 Xinling Road, Shantou 515041, PR China; Department of Pathology and Pathophysiology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Zhejiang Province, PR China.
Department of Pharmaceutical Chemistry, Medical College, Shantou University, 22 Xinling Road, Shantou 515041, PR China.
Biomed Pharmacother. 2017 Jul;91:534-545. doi: 10.1016/j.biopha.2017.04.118. Epub 2017 May 5.
The purpose of this research was to evaluate the protective effects of insulin-loaded poly(ethylene glycol)-b-poly((2-aminoethyl-l-glutamate)-g-poly(l-lysine)) (PEG-b-P(ELG-g-PLL)) on renal ischemia/reperfusion (I/R) injury in rats with diabetes mellitus. Rats were preconditioned with free insulin or insulin/PEG-b-P(ELG-g-PLL) polyplexes, then subjected to renal I/R. The blood and kidneys were then harvested, Glucose uptake rate, glucose transporter 4 (GULT4) mRNA level, cell membrane GULT4 content and GULT4 expression were measured, the level of serum creatinine and blood urea nitrogen were determined, the activity of superoxide dismutase and inducible nitric oxide synthase, the content of malondialdehyde and nitric oxide, reactive oxygen species (ROS) production and nuclear factor κB (NF-κB) mRNA level, Bcl-2 assaciated x protein (Bax) mRNA and B cell lymphoma/lewkmia-2 (Bcl-2) mRNA level, and the expression of protein 47kDa phagocyte oxidase (p47phox) in renal tissues were measured. Insulin preconditioning improved the recovery of renal function, reduced oxidative stress injury, restored nitroso-redox balance and downregulated the expression of p47phox induced by renal I/R injury, while the application of block copolymer PEG-b-P(ELG-g-PLL) as an insulin nanocarrier significantly enhanced the protective effect of insulin. Block copolymer PEG-b-P(ELG-g-PLL) could be used as a potential nanocarrier for insulin with sustained release and enhanced bioavailability.
本研究的目的是评估负载胰岛素的聚（乙二醇）-b-聚（（2-氨基乙基-L-谷氨酸）-g-聚（L-赖氨酸））（PEG-b-P（ELG-g-PLL））对糖尿病大鼠肾缺血/再灌注（I/R）损伤的保护作用。大鼠用游离胰岛素或胰岛素/PEG-b-P（ELG-g-PLL）复合物进行预处理，然后进行肾I/R。随后采集血液和肾脏，测量葡萄糖摄取率、葡萄糖转运蛋白4（GULT4）mRNA水平、细胞膜GULT4含量和GULT4表达，测定血清肌酐和血尿素氮水平，测量超氧化物歧化酶和诱导型一氧化氮合酶活性、丙二醛和一氧化氮含量、活性氧（ROS）生成以及核因子κB（NF-κB）mRNA水平、Bcl-2相关X蛋白（Bax）mRNA和B细胞淋巴瘤/白血病-2（Bcl-2）mRNA水平，以及肾组织中47kDa吞噬细胞氧化酶（p47phox）的表达。胰岛素预处理改善了肾功能的恢复，减轻了氧化应激损伤，恢复了亚硝基氧化还原平衡，并下调了肾I/R损伤诱导的p47phox表达，而应用嵌段共聚物PEG-b-P（ELG-g-PLL）作为胰岛素纳米载体显著增强了胰岛素的保护作用。嵌段共聚物PEG-b-P（ELG-g-PLL）可作为一种潜在的胰岛素纳米载体，具有缓释和提高生物利用度的特点。
