Effects of Nrg4 on myocardial apoptosis of type 2 diabetic rats
SU Jinghua1, WU Fangli2, JIAO Ting3, HAN Ning4, SU Jingke4, ZHANG Haisong3
1. Health Medical Center, 4. Department of Nephrology, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China; 2. Department of Stomatology, Rocket Force Characteristics Medical Center, Beijing 100088, China; 3. Oncology Division, Affiliated Hospital of Hebei University, Baoding 071000, China
Abstract：Objective To investigate the effects of neuregulin 4 (Nrg4) on myocardial apoptosis of type 2 diabetic rats. Methods SD rats were randomly divided into vehicle group, diabetes mellites (DM) group and Nrg4 administration group (Nrg4). The apoptosis rate of myocardial cells was detected by flow cytometry, the expression of Bax and Bcl-2 transcription were detected by qRT-PCR, and the expression of apoptosis-related proteins Bax, Bcl-2 and Cleaved caspase 3 were detected by Western blot. Results Compared with the vehicle group, DM significantly promoted cell apoptosis [(35.49±1.37)% vs. (11.98±0.85)%; P＜0.05], heightened Bax and cleaved-caspase 3 expression, and reduced Bcl-2 expression (P＜0.05). While CBD obviously inhibited cell apoptosis [(19.28±0.96)% vs. (35.49±1.37)%; P＜0.05], reduced Bax and cleaved-caspase 3 expression, and increased Bcl-2 expression (P＜0.05). Conclusions Nrg4 attenuates myocardial apoptosis of type 2 diabetic rats.
Wang L, Cai Y, Jian L, et al. Impact of peroxisome proliferator-activated receptor-α on diabetic cardiomyopathy[J]. Cardiovasc Diabetol, 2021,20(1):2.
[2]
Seferovic P M, Paulus W J. Clinical diabetic cardiomyopathy: a two-faced disease with restrictive and dilated phenotypes[J]. Eur Heart J, 2015,36(27):1718-1727, 1727a.
[3]
Chen Z, Wang G X, Ma S L, et al. Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders[J]. Mol Metab, 2017,6(8):863-872.
[4]
Wang G X, Zhao X Y, Meng Z X, et al. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis[J]. Nat Med, 2014,20 (12): 1436- 1443.
[5]
Zhu B, Mei W, Jiao T, et al. Neuregulin 4 alleviates hepatic steatosis via activating AMPK/mTOR-mediated autophagy in aged mice fed a high fat diet[J]. Eur J Pharmacol, 2020,884:173350.
[6]
Yan P, Xu Y, Zhang Z, et al. Decreased plasma neuregulin 4 levels are associated with peripheral neuropathy in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study[J]. Cytokine, 2019,113:356-364.
[7]
Kocak M Z, Aktas G, Atak B M, et al. Is Neuregulin-4 a predictive marker of microvascular complications in type 2 diabetes mellitus?[J]. Eur J Clin Invest, 2020,50(3):e13206.
[8]
Yan P, Zhang Z, Miao Y, et al. Changes of circulating neuregulin 4 and its relationship with 25-hydroxy vitamin D and other diabetic vascular complications in patients with diabetic peripheral neuropathy[J]. Diabetol Metab Syndr, 2020,12:42.
[9]
Liu M, Xiang G, Lu J, et al. TRAIL protects against endothelium injury in diabetes via Akt-eNOS signaling[J]. Atherosclerosis, 2014,237(2):718-724.
[10]
Wang H, Wang L, Hu F, et al. Neuregulin-4 attenuates diabetic cardiomyopathy by regulating autophagy via the AMPK/mTOR signalling pathway[J]. Cardiovasc Diabetol, 2022,21(1):205.
Gavaldà N A, Villarroya J, Cereijo R, et al. The endocrine role of brown adipose tissue: an update on actors and actions[J]. Rev Endocr Metab Disord, 2022,23(1):31-41.
[17]
Munck T, Boesch M, Verhaegh P, et al. Is there a role for neuregulin 4 in human nonalcoholic fatty liver disease?[J]. PLoS One, 2021,16(5):e251822.
[18]
Li M, Chen Y, Jiang J, et al. Elevated serum neuregulin 4 levels in patients with hyperthyroidism[J]. Endocr Connect, 2019,8(6):728-735.
[19]
Blüher M. Neuregulin 4: a “hotline” between brown fat and liver[J]. Obesity (Silver Spring), 2019, 27(10): 1555-1557.
[20]
Li Y, Jin L, Jiang F, et al. Mutations of NRG4 contribute to the pathogenesis of nonalcoholic fatty liver disease and related metabolic disorders[J]. Diabetes, 2021,70(10):2213-2224.
[21]
Yang F, Zhou N, Zhu X, et al. n-3 PUFAs protect against adiposity and fatty liver by promoting browning in postnatally overfed male rats: a role for NRG4[J]. J Nutr Biochem, 2021,93:108628.
[22]
Tutunchi H, Mobasseri M, Aghamohammadzadeh N, et al. Serum neuregulin 4 (NRG-4) level and non-alcoholic fatty liver disease (NAFLD): a case-control study[J]. Int J Clin Pract, 2021,75(10):e14555.
[23]
Shi J, Xu W, Zheng R, et al. Neuregulin 4 attenuate tubulointerstitial fibrosis and advanced glycosylation end products accumulation in diabetic nephropathy rats via regulating TNF-R1 signaling[J]. Am J Transl Res, 2019,11(9):5501-5513.
[24]
Yang Z, Yaling W, Tao L, et al. Cardioprotective effect of NRG-4 gene expression on spontaneous hypertension rats and its mechanism through mediating the activation of ErbB signaling pathway[J]. Cell Mol Biol (Noisy-le-grand), 2022,68(1):89-101.
2023, Vol. 34 
