Abstract：Objective To investigate the mechanism of intervention of Shenyuan Granules in diabetic nephropathy (DN) based on IRE-1α/NF-κB pathway. Methods Forty SPF grade 7-week-old db/db male mice with body weight of (40±2) g were selected and divided into model group and Shenyuan Granules low-dose, medium-dose, and high-dose groups with ten mice in each group according to random number table method. Ten 7-week-old wild-type WT male mice of the same strain with SPF grade and body weight of (20±2) g were selected as blank control group. After one week of adaptive feeding, fasting blood glucose was detected in model group and Shenyuan Granules low-dose, medium-dose, and high-dose groups, and DN was determined by fasting blood glucose ≥16.7 mmol/L for three consecutive times, urine volume ＞150% of blank control group, and continuous proteinuria. Subsequently, Shenyuan Granules low-dose, medium-dose, and high-dose groups were given 1.5, 3.0, and 6.0 g/(kg·d) Shenyuan Granules intragastrically, respectively, while model group and blank control group were given the same amount of double steam water intragastrically, all five groups were given continuous intragastrically for 12 weeks. After the experiment, five kidney tissues of groups were collected and stained with hematoxylin-eosin to observe the pathological changes of kidney. Real-time polymerase chain reaction was used to detect the mRNA expression of GRP78, XBP-1S, IRE-1α, and NF-κB in the five groups, and the protein expressions of GRP78 and XBP-1S, and the phosphorylation levels of IRE-1α and NF-κB in the five groups were detected by Western blot. Results No obvious lesions were observed in the blank control group, while the model group had abnormal renal tissue structure, glomerular atrophy, and partial renal tubule dilatation. Compared with the model group, Shenyuan Granules low-dose, medium-dose, and high-dose groups showed some improvements. The mRNA expression of GRP78, XBP-1S, IRE-1α, NF-κB, and the protein expression of GRP78, XBP-1S in model group were higher than those in blank control group, and the levels of p-IRE-1α /IRE-1α and p-NF-κB /NF-κB were higher than those in blank control group, the differences were highly statistically significant (P＜0.01). The mRNA expression of GRP78, XBP-1S, IRE-1α, NF-κB, and the protein expression of GRP78, XBP-1S in Shenyuan Granules low-dose, medium-dose, and high-dose groups were lower than those in model group, and the levels of p-IRE-1α/IRE-1α and p-NF-κB/NF-κB were lower than those in model group, the differences were statistically significant (P＜0.05 or P＜0.01). The mRNA expression of GRP78, XBP-1S, IRE-1α, NF-κB, and the protein expression of XBP-1S in Shenyuan Granules high-dose group were lower than those in Shenyuan Granules medium-dose and low-dose groups, and the levels of p-IRE-1α/IRE-1α and p-NF-κB/NF-κB were lower than those in Shenyuan Granules medium-dose and low-dose groups, the protein expression of GRP78 in Shenyuan Granules high-dose group was lower than that in Shenyuan Granules low-dose group; the levels of IRE-1α mRNA, GRP78 protein, XBP-1S protein, and p-IRE-1α/IRE-1α in Shenyuan Granules medium-dose group were lower than those in Shenyuan Granules low-dose group, and the differences were statistically significant (P＜0.05 or P＜0.01). Conclusion Shenyuan Granules may inhibit excessive endoplasmic reticulum stress response through IRE-1α/NF-κB pathway to reduce renal inflammation, improve renal function, and inhibit the progression of DN.
周怡坤 王小琴. 基于IRE-1α/NF-κB通路探讨肾元颗粒干预糖尿病肾病的作用机制[J]. 中国医药导报, 2023, 20(19): 19-23,29.
ZHOU Yikun WANG Xiaoqin. Study on the mechanism of intervention of Shenyuan Granules in diabetic nephropathy based on IRE-1α/NF-κB pathway. 中国医药导报, 2023, 20(19): 19-23,29.
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