2025, Vol. 29 ›› Issue (8): 1593-1599

Correlation between Mer receptor tyrosine kinase and diabetic peripheral neuropathy in Sprague-Dawley rats

Su Xiaoyang1, Chen Wenting1, Fu Yidan1, Zhao Yan1, Lan Danfeng2, Yang Qiuping1   

Abstract: BACKGROUND: The pathogenesis of diabetic peripheral neuropathy has not yet been clarified, and TAM (Tyro3, Axl, and MerTK) receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system.
OBJECTIVE: To investigate the difference of Mer receptor tyrosine kinase (MerTK) levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy, and to study the correlation between MerTK and diabetic peripheral neuropathy.
METHODS: Forty male Sprague-Dawley were randomly divided into control group with 15 rats, type 2 diabetes group with 10 rats, and diabetic peripheral neuropathy group with 15 rats. The control group was fed with ordinary diet, while the experimental groups were fed with high-fat and high-sugar diet. After 6 weeks, intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups. After 14 days, tail vein blood was collected to detect blood glucose. If blood glucose ≥ 16.7 mmol/L, the model of type 2 diabetes was successfully established. Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks. The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia. Blood samples were collected from the abdominal aorta, and the sciatic nerve tissue was collected. Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling. ELISA was used to detect peripheral blood glucose, blood lipids and serum MerTK levels in rats; hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve; immunofluorescence, immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue.
RESULTS AND CONCLUSION: The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed, and the modeling rate of diabetic peripheral neuropathy was 80%. Compared with the control group, the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher (P < 0.000 1), while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group; and the sciatic nerve conduction velocity was significantly decreased (P < 0.05), which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group. Histological examination: Compared with the control group, the sciatic nerve nuclei were reduced in the type 2 diabetes group, with some vacuolar degeneration and phagocytosis; in the diabetic peripheral neuropathy group, the cell body was swollen, the nuclear spacing was increased, vacuolar degeneration was observed, and the myelin sheath was partitioned and unsmooth, and lattice-like axons appeared. Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group. Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group (P < 0.05). To conclude, elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.
Key words: Mer receptor tyrosine kinase, diabetic peripheral neuropathy, biological marker, type 2 diabetes, Sprague-Dawley rat