Effect of pravastatin on functional recovery from sciatic nerve crush injury in rats

Liu Zan; An Ran; Li Baocheng

doi:10.12307/2025.248

Abstract：BACKGROUND:Pravastatin is a clinically effective drug for the treatment of hypercholesterolemia and is now found to play a beneficial role in the treatment of CNS injury;however,the mechanism remains unknown. OBJECTIVE:To ascertain the possible mechanism of action and whether pravastatin medication can expedite functional recovery following sciatic nerve crush injury. METHODS:Male Sprague-Dawley rats were randomly assigned into:pravastatin(sciatic nerve crush injury+pravastatin gavage),negative control(sciatic nerve crush injury+saline gavage),and sham operation(sciatic nerve exposure but no injury+saline gavage).While the other two groups received comparable amounts of saline gavage,the pravastatin group received postoperative pravastatin(5 mg/kg)by gavage for 1 week.The general conditions of the rats in each group were observed after operation.Sciatic function index was evaluated at the end of the 2nd,4th,6th,and 8th week after operation,and the wet mass ratio of the gastrocnemius muscle was measured at the end of the 8th week after operation.The levels of inflammatory cytokines in serum were measured using ELISA.Histomorphometrics was used to measure the number of myelinated nerve fibers,fiber diameter,axon diameter,and myelin sheath thickness.RT-qPCR assay was used to measure the relative mRNA expression of nerve growth factor and brain-derived neurotrophic factor,and western blot was used to measure the protein expression of growth-associated protein 43. RESULTS AND CONCLUSION:Compared with the negative control group,the sciatic function index in the pravastatin group recovered faster(P<0.05)and was closer to the level of the sham operation group,the expression of tumor necrosis factor α and interleukin 6 in serum was lower(P<0.05)and close to that of the sham operation group,and the relative mRNA expression of nerve growth factor and brain-derived neurotrophic factor in the sciatic nerve increased(P<0.05 or P<0.01),the relative protein expression of growth-associated protein 43 in the sciatic nerve was also significantly increased(P<0.05),the number of myelinated nerve fibers was increased more,and the values of fiber diameter,axon diameter,and myelin sheath thickness were larger(P<0.01)and closer to those of the sham operation group.To conclude,treatment with pravastatin accelerates functional recovery from sciatic nerve crush injury by a possible mechanism of inhibiting the expression of tumor necrosis factor α and interleukin 6 and promoting the secretion of neurotrophic factors nerve growth factor and brain-derived neurotrophic factor.