Role of spinal SGK-1/Kalirin-7/NR2B signaling pathway in type 2 diabetic neuropathic pain in rats
10.3760/cma.j.cn131073-20240507-00113
- VernacularTitle:脊髓SGK-1/Kalirin-7/NR2B信号通路在大鼠2型糖尿病神经病理性痛中的作用
- Author:
Jiali CHEN
1
;
Maobiao ZHANG
1
;
Hong CAO
1
;
Jun LI
1
Author Information
1. 温州医科大学附属第二医院 育英儿童医院麻醉与围术期医学科，温州 325024
- Publication Type:Journal Article
- Keywords:
Rho Guanine nucleotide exchange factors;
Receptors, N-methyl-D-aspartate;
Diabetes mellitus, type 2;
Diabetic neuropathies;
Serum and glucocorticoid-induc
- From:
Chinese Journal of Anesthesiology
2025;45(1):65-70
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of spinal serum and glucocorticoid-inducible kinase 1(SGK-1)/Kalirin-7/N-methyl-D-aspartate receptor 2B(NR2B) signaling pathway in the type 2 diabetic neuropathic pain(DNP) in rats.Methods:Clean-grade male Sprague-Dawley rats, aged 6 weeks, weighing 120-160 g, were randomized to receive a normal diet(normal control group [group C, n=12]) or a high-fat and high-glucose diet( n=60). Diabetes mellitus was induced by single intraperitoneal injection of streptozotocin 35 mg/kg after 8 weeks of a high-fat and high-glucose diet. The successful DNP model was defined as a decrease in the pain threshold(mechanical paw withdrawal threshold [MWT] and thermal paw withdrawal latency [TWL]) to less than 85% of the baseline value in type 2 diabetic rats. Twelve non-DNP(pain threshold above 85% of the baseline value) rats with type 2 diabetes mellitus were randomly selected and included in non-DNP group(NDNP group). Thirty-six rats with DNP were divided into 3 groups( n=12 each) using a random number table method: DNP group, DNP plus SGK1 inhibitor GSK-650394 group(DNP+ G group), and DNP plus solvent control group(DNP+ SC group). At day 14 after STZ injection, GSK-650394(10 μl) 300 nmol/L was intrathecally injected once a day for 14 consecutive days in DNP+ G group. DNP group did not receive any treatment, and the rats in DNP+ SC group received intrathecal injection of the equal volume of dimethyl sulfoxide. The MWT and TWL were measured after 8 weeks of feeding, at 14 days after STZ injection, and at 3, 7 and 14 days after intrathecal injection(at 17, 21 and 28 days after STZ injection). After 7 days of intrathecal injection, the lumbar enlargement tissues of the spinal cord were collected for determination of the expression of SGK-1, phosphorylated SGK-1(Ser422-SGK1), Kalirin-7, phosphorylated NR2B(Tyr1472-NR2B), and NR2B by Western blot. The ratios of Ser422-SGK1 to SGK1 and Tyr1472-NR2B to NR2B were calculated. Results:Compared with C group, the MWT was significantly decreased and TWL was shortened at 14 days after STZ injection and at the corresponding time points of intrathecal injection, and the ratios of spinal Ser422-SGK1 to SGK1 and Tyr1472-NR2B to NR2B were increased, and the expression of Kalirin-7 was up-regulated in DNP group( P<0.05), and no statistically significant change was found in the aforementioned parameters in NDNP group( P>0.05). Compared with DNP group, the MWT was significantly increased and TWL was prolonged at 3, 7 and 14 days of intrathecal injection, the ratios of Ser422-SGK1 to SGK1 and Tyr1472-NR2B to NR2B in the spinal cord tissue were decreased, Kalirin-7 expression was down-regulated( P<0.05), and no statistically significant differences were found in the aforementioned parameters in DNP+ SC group( P>0.05). Conclusions:The enhanced phosphorylation of SGK-1 in the spinal cord of DNP rats may play an important role in the occurrence and maintenance of DNP probably by activating the Kalirin-7/NR2B signaling pathway.
