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| Study on the mechanism of Sanhuang Yishen Capsule in inhibiting apoptosis of renal tissue cells in DKD rats based on IRE1/ GPR78 signaling pathway |
| Hits 168 Download times 121 Received:January 22, 2024 |
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| DOI
10.11656/j.issn.1672-1519.2024.05.17 |
| Key Words
Sanhuang Yishen Capsule;diabetic kidney disease;endoplasmic reticulum stress;apoptosis;IRE1/GPR78 signaling pathway |
| Author Name | Affiliation | E-mail | | ZHANG Hui | Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061001, China | | | LYU Shuquan | Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061001, China | czlvshuquan@163.com | | PAN Baochao | Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061001, China | |
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| Abstract
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| [Objective] To investigate the therapeutic effect of Sanhuang Yishen Capsule on diabetic kidney disease （DKD） model rats， and to study the effect of Sanhuang Yishen Capsule on IRE1/GPR78 signaling pathway in DKD model rats. [Methods] The 30 rats were divided into the normal group，model group，positive drug group，Sanhuang Yishen low dose group，and Sanhuang Yishen high dose group，6 rats in each group. Except for the normal group，the DKD model was established by a high-sugar and high-fat diet combined with streptozotocin （STZ） injection in the other groups. After modeling，the normal group and the model group were given normal saline every day，the positive drug group was given irbesartan 11.51 mg/kg every day，and Sanhuang Yishen low dose and Sanhuang Yishen high dose groups were given Sanhuang Yishen Capsule 0.81 g/kg and 1.62 g/kg respectively every day for 4 weeks. The therapeutic effect of Sanhuang Yishen Capsule on DKD was evaluated by observing the blood glucose and body weight levels of rats in each group during administration，detecting the levels of biochemical indicators，and renal histopathological staining after administration. Secondly，the effects of Sanhuang Yishen Capsule on oxidative stress and inflammatory factors in renal tissue of DKD rats were studied by kit and ELISA. Finally，the effects of Sanhuang Yishen Capsule on renal cell apoptosis and IRE1/GPR78 signaling pathway in DKD rats were studied by immunofluorescence，Tunel staining，and Western blot. [Results] After the intervention of Sanhuang Yishen Capsule，the body weight of DKD rats increased significantly，the blood glucose level decreased，the levels of serum creatinine （Cr），urea nitrogen（BUN） and 24-hour urine protein decreased，and the pathological changes of renal tissue in DKD rats were improved. The infiltration of inflammatory cells and fibrosis in renal tissue were reduced. In addition，Sanhuang Yishen Capsule can significantly increase the activity of SOD and GSH-Px in renal tissue of DKD model rats，reduce the level of MDA，and reduce the levels of IL-6，IL-1β，and TNF-α in the serum of DKD rats. Western blot results showed that Sanhuang Yishen Capsule significantly reduced the protein expression levels of endoplasmic reticulum stress marker factors GRP78 and IRE1 in renal tissue of DKD model rats，and effectively reduced the expression of pro-apoptotic proteins Bax，Caspase-3，and Caspase-9 in renal tissue of model rats，and increased the expression of anti-apoptotic protein BCL2. [Conclusion] Sanhuang Yishen Capsule has a significant therapeutic effect on DKD model rats，and its mechanism may be related to inhibiting the activation of the IRE1/GPR78 signaling pathway in renal tissue and improving endoplasmic reticulum stress. |
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