Role Of ERK In Change Of AChR During Resistance To Rocuronium In Skeletalmuscles Of Burned Rats

Objective:Thermal injury,neuron damage and acute and critical diseases could lead to denervation-like change.Denervation could lead to low potency to nondepolarizing muscle relaxants as the resistence to nondepolarizing muscle relaxants.The resistence is resulted from the up-regulation of acetylcholine receptors(ACh Rs)in neuromuscular junction.The Ras/ERK signaling pathway has been proved to be a key role in the up-regulation of Ach Rs.The action of Ras/ERK signaling pathway will lead to the up-regulation of each subunits of Ach Rs.The study is to evaluate the effect of Ras/ERK signaling pathway in thermal injury-induced resistance to rocuronium in rats for clinical prevention and treatment.Method:Thirty male SPF Sprague-Dawley rats,weighing 230-250 g,aged 7-9 weeks,were randomly divided into 3 groups(n=10 each)using a random number table: Control group,Burn group and Burn+U0126 group.Thermal injury was produced by hot solid.The surface of tibialis anterior muscle were shaved.A hot brass block at 95°C was applied for 12 s on the skin over the tibialis anterior muscle of the right legs in Burn group and Burn+U0126 group.U0126 15 mg/kg was injected in Burn+U0126 group and same volume of DMSO was injected in Control and Burn group.The anterior tibial was isolated at day 7 after operation for determination of the expression of fetal ACh R subunit(?-ACh R)and adult ACh R subunit(?-ACh R)and tension test.Result:The expression of ?-ACh R of the muscle was significantly higher in B group than in C group and U group(P<0.05).There is no significant difference between three groups on the expression of ?-ACh R(P > 0.05).Compared with C group,the concentration-effect curve of B group was shifted to the right,the half inhibitory concentration was significantly increased.Compared with B group,the concentration-effect curve of U group was shifted to the left,the half inhibitory concentration was significantly decreased.Conclusion:The action of Ras/ERK signaling pathway will lead to the up-regulation of Ach Rs and resistence of rocuronium.Blocking the Ras/ERK signaling pathway could reduce the resistance to the muscle of thermal injuried rat.