Protective effect of cannabidiol on high glucose-induced podocytes MPC5 apoptosis
SU Jinghua1, JIAO Ting2, HAN Ning3, SU Jingke3, DANG Ruijie4, LI Lin4, ZHANG Haisong2
1. Health Medical Center, 3. Department of Nephrology, the Third Medical Center of Chinese PLA General Hospital,Beijing 100039, China;
2. Oncology Division, Affiliated Hospital of Hebei University, Baoding 071000, China;
4. Medical School of Chinese PLA, Beijing 100853, China
目的 探讨大麻二酚(cannabidiol, CBD)对高糖环境中小鼠足细胞系MPC5细胞凋亡的影响。方法 将MPC5细胞分为对照组(Vehicle)、高糖组(high glucose, HG)和CBD组。CCK-8试剂盒检测MPC5细胞的增殖活性,流式细胞术检测MPC5细胞的凋亡率,Western blot检测裂孔膜蛋白Nephrin与凋亡相关蛋白Bax及Bcl-2的表达情况。结果 与Vehicle组相比,HG组明显抑制MPC5增殖并促进其凋亡[(25.27±2.15)% vs. (8.43±0.70) %];而CBD干预显著促进高糖环境中MPC5增殖且抑制凋亡[(12.83±1.05)% vs. (25.27±2.15) %; P<0.05]。同时,CBD干预显著升高高糖环境中MPC5细胞Nephrin蛋白的表达[(0.77±0.06) vs. (0.32±0.10)],降低促凋亡蛋白Bax与抗凋亡蛋白Bcl-2的蛋白表达比[(1.02±0.09) vs. (12.30±0.09)]。结论 CBD能缓解高糖诱导的MPC5细胞凋亡。
Objective To investigate the effect of cannabidiol (CBD) on podocytes MPC5 apoptosis induced by high glucose.Methods MPC5 cells were randomly divided into vehicle group, high glucose (HG) group and CBD group. CCK-8 method was used to access cell proliferation, flow cytometry was used to evaluate apoptotic rate, and western blot was used to investigate protein level of Nephrin and apoptosis-related proteins Bax and Bcl-2.Results Compared with the Vehicle group, HG significantly inhibited MPC5 proliferation and promoted MPC5 apoptosis [(25.27±2.15)% vs. (8.43±0.70)%], while CBD obviously promoted MPC5 proliferation and inhibited MPC5 apoptosis [(12.83±1.05)% vs. (25.27±2.15)%; P<0.05] in the high glucose environment. Meanwhile, CBD administration increased Nephrin expression [(0.77±0.06) vs. (0.32±0.10)], and reduced Bax/Bcl-2 [(1.02±0.09) vs. (12.30±0.09); P<0.05].Conclusions CBD attenuates high glucose-induced MPC5 apoptosis.
He M, Li Y, Wang L, et al. MYDGF attenuates podocyte injury and proteinuria by activating Akt/BAD signal pathway in mice with diabetic kidney disease[J]. Diabetologia, 2020,63(9):1916-1931.
[4]
Fouda M A, Ruben P C. Protein kinases mediate anti-inflammatory effects of cannabidiol and estradiol against high glucose in cardiac sodium channels[J]. Front Pharmacol, 2021,12:668657.
Rajesh M, Mukhopadhyay P, Bátkai S, et al. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy[J]. J Am Coll Cardiol, 2010,56(25):2115-2125.
[7]
Lehmann C, Fisher N B, Tugwell B, et al. Experimental cannabidiol treatment reduces early pancreatic inflammation in type 1 diabetes[J]. Clin Hemorheol Microcirc, 2016,64(4):655-662.
[8]
Fouda M A, Ghovanloo M R, Ruben P C. Cannabidiol protects against high glucose-induced oxidative stress and cytotoxicity in cardiac voltage-gated sodium channels[J]. Br J Pharmacol, 2020,177(13):2932-2946.
[9]
Mei W, Zhu B, Shu Y, et al. GDF11 protects against glucotoxicity-induced mice retinal microvascular endothelial cell dysfunction and diabetic retinopathy disease[J]. Mol Cell Endocrinol, 2021,537:111422.
[10]
Susztak K, Raff A C, Schiffer M, et al. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy[J]. Diabetes, 2006,55(1):225-233.
[11]
Chuang P Y, Yu Q, Fang W, et al. Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor[J]. Kidney Int, 2007,72(8):965-976.
Gruden G, Barutta F, Kunos G, et al. Role of the endocannabinoid system in diabetes and diabetic complications[J]. Br J Pharmacol, 2016,173(7):1116-1127.
[14]
Jourdan T, Szanda G, Rosenberg A Z, et al. Overactive cannabinoid 1 receptor in podocytes drives type 2 diabetic nephropathy[J]. Proc Natl Acad Sci U S A, 2014,111(50):E5420-E5428.
[15]
Barutta F, Corbelli A, Mastrocola R, et al. Cannabinoid receptor 1 blockade ameliorates albuminuria in experimental diabetic nephropathy[J]. Diabetes, 2010,59(4):1046-1054.
[16]
Barutta F, Piscitelli F, Pinach S, et al. Protective role of cannabinoid receptor type 2 in a mouse model of diabetic nephropathy[J]. Diabetes, 2011,60(9):2386-2396.
[17]
Janiak P, Poirier B, Bidouard J P, et al. Blockade of cannabinoid CB1 receptors improves renal function, metabolic profile, and increased survival of obese Zucker rats[J]. Kidney Int, 2007,72(11):1345-1357.