Effects of carnosine on ferroptosis and inflammatory responses in STZ⁃induced diabetic mice
10.19405/j.cnki.issn1000-1492.2023.08.013
- Author:
Song Zhang
1
;
Xueqi Liu
1
;
Ling Jiang
1
;
Yonggui Wu
1
Author Information
1. Dept of Nephrology , The First Afiliated Hospital of Anhui Medical University, Hefei 230022
- Publication Type:Journal Article
- Keywords:
diabetic nephropathy;
ferroptosis;
inflammation;
carnosine
- From:
Acta Universitatis Medicinalis Anhui
2023;58(8):1322-1328
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the effects of carnosine (CAR) on streptozotocin (STZ) induced renal feroptosis and inflammation in diabetic mice .
Methods :Type 1 diabetes mice model were induced by STZ , and normal C57 mice were used as normal control group . The C57 mice were divided into 5 groups (6 - 8 mice in each group) : normal control group (NC) , normal control + carnosine group (NC + CAR) , STZ model group (STZ) ,STZ model + carnosine group (STZ + CAR) , STZ model + ferroptosis inhibitor group (STZ + Fer⁃1) . After feeding the mice for 16 weeks , serum samples were collected to detect blood creatinine ( CRE) and urea nitrogen ( BUN) levels . The urine of mice was collected to detect the 24 - hour urinary albumin level . HE staining and PAS staining were performed to observe the degree of renal pathological injury . Real⁃time PCR was used to detect the expression of interleukin (IL) Ⅳ1β , IL⁃6 , monocyte chemotactic protein 1(MCP⁃1) and tumor necrosis factor⁃α (TNF⁃α ) in mouse kidney tissue . The expression of reactive oxygen species(ROS) in mouse kidney was detected by immunofluorescence . Morphology of renal mitochondria was observed by transmission electron microscopy . The protein expression levels of glutathione peroxidase 4(GPX 4) and long⁃chain lipoacyl⁃CoA synthetase 4( ACSL4) , which are ferroptosis indexes , were detected by Western blot . The contents of malondialdehyde ( MDA) , glutathione ( GSH) and Fe2 + in mouse kidney tissue were determined .
Results :Compared with NC group , CRE and BUN levels in STZ group increased (P < 0. 001) ; and ompared with STZ group , these indexes decreased in STZ + CAR group (P < 0. 001 , P < 0. 01) . Renal histopathological examination showed that compared with NC group , renal tubule dilatation , inflammatory cell infiltration and glycogen deposition significantly increased in STZ group ; and compared with STZ group , tubule dilatation , inflammatory cell infiltration and glycogen deposition decreased in STZ + CAR group . Electron microscope results showed that the renal mitochondria in STZ group were swollen , membrane density increased , mitochondrial ridges decreased or absent , renal tubule dilation was improved significantly in the STZ + CAR group and STZ + Fer⁃1 group , and inflammatory cell infiltration was reduced . Real⁃time PCR test results showed that compared with NC group , mRNA expression levels of inflammatory factor (IL⁃1β , IL⁃6 , MCP⁃1 and TNF⁃α ) increased in STZ group (P < 0. 001 or P < 0. 01) ; and mRNA expressions of IL⁃1β , IL⁃6 , MCP⁃1 and TNF⁃α were decreased in STZ + CAR group compared with STZ group (P < 0. 01 or P < 0. 05) . Immunofluorescence results showed that compared with NC group , ROS level in kidney tissue of mice in STZ group increased (P < 0. 001) ; and compared with STZ group , the expression of ROS in kidney tissue of STZ + CAR group decreased while ROS expression in STZ + CAR group decreased ( P < 0. 01) . Compared with NC group , GPX4 expression and GSH content in kidney of STZ group decreased ( P < 0. 001) , and ACSL4 protein expression and MDA and Fe2 + contents increased (P < 0. 01 or P < 0. 001) , GPX4 expression and GSH content increased (P < 0. 01) , ACSL4 protein expression and MDA and Fe2 + content decreased in STZ + CAR group (P < 0. 01 or P < 0. 001) .
Conclusion : CAR inhibits ferroptosis and inflammation in the kidney in diabetic mice induced by STZ ,
and improved renal pathological injury in diabetic mice .
- Full text:2024081616383678839肌肽对链脲佐菌素诱导的糖尿...小鼠肾脏铁死亡和炎症的影响_张崧.pdf
