Objective: This study evaluated the effect and molecular mechanism of pancreatic kallikrein (PKK) in improving mechanical allodynia in STZ-induced C57 mice, an animal model of type 1 diabetes, based on CX3CL1/CX3CR1 pathway.
Methods: Male C57 mice, weighing 20-23g, were fasted overnight for 12h (20:00-8:00 next day) and injected with STZ (100mg/kg) to induce type 1 diabetes model. 24 diabetic mice were divided into PKK-1 group (PKK 6u/kg/d, ip, n=8), PKK-2 group (PKK 60u/kg/d, ip, n=8) and DNS group (0.9% NaCl 0.15ml/d, ip, n=8). Eight normal C57 mice were injected with PKK (6u/kg/d, ip) as the NPK group. The mechanical allodynia of each group was evaluated from 1h to 5 weeks after PKK injection. The expression of CX3CL1/CX3CR1 at the lumbar spinal cord was also measured at the 5th week using Western Blot analysis.
Results: 1) More than 80% of C57 mice were tested FBG>11.1mmol/L at the 7th day after STZ injection and divided into the diabetic group. 2) Compared with the normal mice, we showed that the diabetic mice developed mechanical allodynia at the early stage of diabetes. Meanwhile, The intraperitoneal injection of PKK could decrease such mechanical allodynia in a dose-independent manner. 3) Compared with the DNS group, the intraperitoneal injection of PKK significantly attenuated the expression of CX3CL1/CX3CR1 at the dorsal horn.
Conclusion: Our previous study indicated that the CX3CL1/CX3CR1 pathway played an important role in the progress of painful diabetic neuropathy. These results showed that intraperitonea injection of PKK significantly decreased mechanical allodynia and attenuated the expression of CX3CL1/CX3CR1 at the dorsal horn. This study may contribute to a better understanding of the therapeutic effect and mechanism of PKK on painful diabetic neuropathy.
X. Xiang: None. J. Hui: None. X. Lan: None.