Full
Outline
To investigate the protective effect and mechanism of Schisandrae Mixture（五味子合剂，SM）on the kidneys of diabetic nephropathy（DN）rats.
Sixty male SPF SD rats were randomly divided into control group，model group，dapagliflozin（DA）group，SM high-dose（SM-H）group，SM medium-dose（SM-M）group and SM low-dose（SML）group.The model was induced by a high-sugar and high-fat diet combined with streptozotocin（STZ）.Blood glucose（Glu）and 24-hour urinary protein（24 h UTP）were measured every 4 weeks.After 12 weeks of administration，the kidney was weighed，the serum and kidney tissue were collected，and the kidney index（KI）was calculated.The levels of serum creatinine（Scr）and blood urea nitrogen（BUN）were detected.Hematoxylin-eosin（HE），silver hexamine（PASM）and Masson staining were used to observe the pathological morphology of renal tissue.The levels of malondialdehyde（MDA），superoxide dismutase（SOD）and glutathione（GSH）in renal tissue were detected by corresponding kits.The mRNA and protein expression of hypoxia-inducible factor-1α（HIF-1α）and heme oxygenase-1（HO-1）in renal tissue were detected by real-time fluorescence quantitative PCR（qRT-PCR）and Western Blotting（WB）.The levels of glutathione peroxidase 4（GPX4）and acyl-CoA synthetase long-chain family member 4（ACSL4）in renal tissue were detected by immunohistochemistry.
Compared with those of the control group，the pathological damage of the model group was significantly aggravated；the levels of Glu，24 h UTP，Scr，BUN and KI were significantly increased，MDA level was significantly increased，the levels of SOD and GSH were significantly decreased，HIF-1αand HO-1 protein and mRNA expression levels were significantly increased，GPX4 expression level was significantly decreased，ACSL4 expression level was significantly increased（P<0.05）. Compared with those of the model group，the pathological damage of DA group and SM group was significantly reduced；the levels of Glu，24 h UTP，Scr，BUN and KI were decreased，the level of MDA in renal tissue was decreased，and the levels of SOD and GSH were increased.Among them，the changes of the above indexes in SM-H group were the most obvious，and there was statistical significance except for BUN，MDA and SOD in SM-L group（P<0.05）.The protein and mRNA levels of HIF-1αand HO-1 in the SM-H group were significantly increased，the expression level of GPX4 was significantly increased，and the expression level of ACSL4 was significantly decreased（P<0.05）.
SM has a certain renal protective effect on DN，which may be related to regulating HIF-1α/HO-1 pathway to reduce oxidative stress and regulating GPX4/ACSL4 pathway to inhibit ferroptosis.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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