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| Shizhi Prescription regulating endoplasmic reticulum stress-related proteins to ameliorate renal injury in hyperuricemic mice by activating Sirt1-Foxo1 pathway |
| Hits 393 Download times 245 Received:June 08, 2023 |
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| DOI
10.11656/j.issn.1672-1519.2023.09.13 |
| Key Words
Shizhi Prescription;hyperuricemia;Sirt1-Foxo1 pathway;endoplasmic reticulum stress |
| Author Name | Affiliation | E-mail | | YANG Feng | Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Nephropathy Institute of Chinese Medicine of Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases of Ministry of Education of Shanghai University of Traditional Chinese Medicine, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China | | | WANG Chuanxu | Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Nephropathy Institute of Chinese Medicine of Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases of Ministry of Education of Shanghai University of Traditional Chinese Medicine, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China | | | WU Zhiyuan | Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Nephropathy Institute of Chinese Medicine of Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases of Ministry of Education of Shanghai University of Traditional Chinese Medicine, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China | | | ZHANG Xuming | Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Nephropathy Institute of Chinese Medicine of Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases of Ministry of Education of Shanghai University of Traditional Chinese Medicine, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China | | | GAO Jiandong | Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Nephropathy Institute of Chinese Medicine of Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases of Ministry of Education of Shanghai University of Traditional Chinese Medicine, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China | jiandong.gao@shutcm.edu.cn |
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| Abstract
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| [Objective] To observed the effects of Shizhi Prescription（SZF） on endoplasmic reticulum stress-related proteins and downstream molecules Chop/Caspase12 in the kidney tissues of hyperuricemic mice to explore its mechanism based on the Sirt1-Foxo1 pathway. [Methods] Thirty-two SPF male BALB/c mice were randomly divided into normal group，model group，febuxostat group and SZF group. The normal group was gavaged with saline，the other groups were gavaged with 250 mg/kg potassium oxyzincate to prepare the HUA mouse model. The febuxostat and SZF groups were given 6 mg/kg and 562.5 mg/kg gavage respectively，the normal and model groups were given the same volume of saline for 2 weeks. In vitro experiments were performed with HK2 cells. Divided into normal group，model group and SZF group. The 200 μg/mL uric acid and 300 μg/mL SZF were treated after 24 h of starvation to intervene for 24 h. Histopathological changes of mouse kidney were observed by HE and Masson staining. Sirt1，IRE1α，Foxo1，Caspase12 and Chop were detected by Western blot and immunohistochemical staining. Western blot and immunofluorescence staining to detect Sirt1，IRE1α，Foxo1，Caspase12 and Chop expression in HK2 cells. [Results] The results of HE staining and Masson staining showed that the tubular wall was thinner，the lumen was dilated，inflammatory cells were infiltrated，and the interstitial fibrous tissue was proliferated in the model group compared with the normal group. Western blot showed that the expression of IRE1α，Foxo1，Caspase12 and Chop was significantly higher in the model group compared with the normal group（P＜0.01 or P＜0.001）. Sirt1 protein expression was significantly decreased（P＜0.001）. Compared with the model group. IRE1α，Foxo1，Caspase12，Chop protein expression was significantly decreased（P＜0.05 or P＜0.001） and Sirt1 protein expression was significantly increased（P＜0.001） in kidney tissues and HK2 cells in the drug-administered group. Immunohistochemical staining and immunofluorescence staining results were consistent with Western blot results. [Conclusion] The mechanism of alleviating renal pathological injury by SZF may be related to the inhibition of endoplasmic reticulum stress and activation of Sirt1-Foxo1 pathway in the renal tissue of HUA mice. |
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