利拉鲁肽对2型糖尿病肾病大鼠细胞焦亡、炎症细胞浸润及对NF-κB通路的影响

doi:10.3969/j.issn.1007-3205.2024.02.015

摘要/Abstract

摘要： 目的探究利拉鲁肽（liraglutide，LIR）对2型糖尿病肾病（diabetic nephropathy，DN）大鼠细胞焦亡、炎症细胞浸润及对核因子κB（nuclear factor-κB，NF-κB）通路的影响。
方法选取45只大鼠，随机选取10只为对照组，其余35只大鼠建立DN模型，30只大鼠建模成功，并随机分为3组（DN组及LIR高、LIR低剂量组），各10只。LIR低、高剂量组分别给予LIR 100、200 g·kg-1·d-1，对照组及DN组给予等量的生理盐水。连续灌胃给药2周后，测量大鼠肾功能指标血清炎症因子水平，炎症细胞计数评估炎症细胞浸润情况，TUNEL染色法检测DNA损伤情况；检测细胞焦亡相关蛋白天冬氨酸特异性半胱氨酸蛋白酶1（Caspase-1）、白细胞介素1β（interleukin-1β，IL-1β）、白细胞介素18（interleukin-18，IL-18）及NF-κB通路相关蛋白的表达量。
结果〖JP2〗与对照组比较，DN组空腹血糖（fasting blood glucose，FBG）、24 h尿蛋白（urine total protein，UTP）及血尿素氮（blood urea nitrogen，BUN）、肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）、白细胞介素1β（interleukin-1β，IL-1β）、及白细胞介素6（interleukin-6，IL-6）水平升高，炎症细胞计数增多，TUNEL阳性细胞率升高，Caspase-1、IL-1β、IL-18、Toll样受体4（Toll like receptor 4，TLR4）、p-NF-κB/NF-κB及核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）蛋白表达上调（P＜0.05）；与DN组比较，LIR低、高剂量组FBG、UTP及BUN水平降低，TNF-α、IL-1β及IL-6水平降低，炎症细胞计数减少，TUNEL阳性细胞率降低，Caspase-1、IL-1β、IL-18、TLR4、p-NF-κB/NF-κB及NLRP3蛋白表达下调（P＜0.05）；与LIR低剂量组比较，LIR高剂量组FBG、UTP及BUN水平降低，TNF-α、IL-1β及IL-6水平降低，炎症细胞计数减少，TUNEL阳性细胞率降低，Caspase-1、IL-1β、IL-18、TLR4、p-NF-κB/NF-κB及NLRP3蛋白表达下调（P＜0.05）。
结论 LIR能够改善2型DN大鼠炎症细胞浸润，抑制细胞焦亡，其作用机制可能抑制NF-κB通路有关。

关键词: 糖尿病肾病, 利拉鲁肽, NF-κB

Abstract: Objective To investigate the effects of liraglutide (LIR) on pyroptosis, inflammatory cell infiltration and nuclear factor-κB (NF-κB) pathway in rats with type 2 diabetic nephropathy (DN).
Methods A total of 45 rats were selected, from which 10 were randomly selected as control group, and the other 35 rats were used to establish DN model. A total of 30 rats were used to estabolish models sucecessfully and randomly divided into three groups (DN group, high-dose LIR group and low-dose LIR group), with 10 rats in each group. High- and low-dose LIR groups were given LIR100 and 200 g·kg-1·d-1, respectively, while control group and DN group were given the same amount of normal saline. After 2 weeks of continuous intragastolic administration, renal function indexes and the serum inflammatory factors were measured, and the inflammatory cell infiltration was evaluated by inflammatory cells. DNA damage was detected by TUNEL staining, and the expression levels of Caspase-1, interleukin-1β (IL-1β), interleukin-18 (IL-18), NF-κB pathway related proteins were detected.
Results Compared with the control group, the levels of fasting blood glucose(FBG), 24 h urine total protein (UTP), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), IL-1β, interleukin-6 (IL-6), the number of inflammatory cells, and the rate of TUNEL positive cells in DN group were increased, and the protein expressions of Caspase-1, IL-1β, IL-18, Toll like receptor 4 (TLR4), P-NF-κB/NF-κB and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) were up-regulated (P＜0.05). Compared with DN group, the levels of FBG, UTP and BUN, TNF-α, IL-1β and IL-6, inflammatory cell count and TUNEL positive cell rate were decreased in low-dose and high-dose LIR groups, and the expression of Caspase-1, IL-1β, IL-18, TLR4, P-NF-κB/NF-κB and NLRP3 protein were decreased (P＜0.05). Compared with low-dose LIR group, the levels of FBG, UTP and BUN, TNF-α, IL-1β and IL-6, inflammatory cell count and TUNEL positive cell rate were decreased in high-dose LIR group, and the expression of Caspase-1, IL-1β, IL-18, TLR4, P-NF-κB/NF-κB and NLRP3 protein were decreased (P＜0.05).
Conclusion LIR can improve inflammatory cell infiltration and inhibit pyroptosis in type 2 DN rats, and its mechanism may be related to inhibition of NF-κB pathway.

Key words: diabetic nephropathies, liraglutide, NF-kappa B

陈亚晖, 杜海波, 冯向峰. 利拉鲁肽对2型糖尿病肾病大鼠细胞焦亡、炎症细胞浸润及对NF-κB通路的影响 [J]. 河北医科大学学报, 2024, 45(2): 208-214.

CHEN Ya-hui, DU Hai-bo, FENG Xiang-feng. Effects of liraglutide on pyroptosis, inflammatory cell infiltration and NF-κB pathway in rats with type 2 diabetic nephropathy[J]. Journal of Hebei Medical University, 2024, 45(2): 208-214.

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利拉鲁肽对2型糖尿病肾病大鼠细胞焦亡、炎症细胞浸润及对NF-κB通路的影响

Effects of liraglutide on pyroptosis, inflammatory cell infiltration and NF-κB pathway in rats with type 2 diabetic nephropathy

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