Effect of curcumin on lidocaine-induced nerve injury in rats: the role of Akt and ERK1∕2 signaling pathway / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of curcumin on lidocaine-induced nerve injury and the role of protein kinase B ( Akt) and extracellular signal-regulated kinase 1∕2 ( ERK1∕2) signaling pathway in rats. Methods Eighty SPF male Sprague-Dawley rats, aged 8-10 weeks, weighing 220-250 g, were di-vided into 8 groups ( n=10 each) using a random number table method: control group ( group C) , sham operation group (group S), lidocaine group ( group L), dimethyl sulfoxide ( DMSO) group, low-dose curcumin group ( group CL ) , high-dose curcumin group ( group CH ) , curcumin plus ERK inhibitor PD98059 group (group P) and curcumin plus Akt inhibitor MK-2206 group (group M). The model of nerve injury was established by injecting 2％ lidocaine 10μl via the catheter in anesthetized rats in the other six groups except for C and S groups. Drugs were injected through a microcatheter for 14 consecutive days starting from 3rd day after IT catheterization as follows DMSO 10μl, curcumin 100μg∕10μl and curcu-min 500 μg∕10 μl were injected once a day in D, CL and CH groups, respectively; curcumin 500 μg∕10μl was injected once a day, and D9805910μg and MK-220612μg ( in 5μl DMSO) were intraperitoneal-ly injected once a week in P and M groups, respectively. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal threshold ( TWL) on the operated side were measured on 1 day before IT catheterization, before administration on 3rd day after IT catheterization, and on 14th day after adminis-tration. The spinal cord was removed on 1st day after the end of administration for determination of the ex-pression of ERK1∕2, phosphorylated ERK1∕2 (p-ERK1∕2), Akt, phosphorylated Akt (p-Akt), c-fos, Bcl-2 and Bax ( by Western blot) and expression of ERK1∕2 and Akt mRNA ( by real-time polymerase chain reaction) . Results Compared with group C, the MWT was significantly decreased, the TWL was short-ened, the expression of ERK1∕2 protein and mRNA, p-ERK1∕2, c-fos, Akt protein and mRNA, p-Akt and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group L (P<0. 05). Com-pared with group L, the MWT was significantly increased, and the TWL was prolonged in CL, CH, P and M groups, the expression of p-ERK1∕2, c-fos, p-Akt and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in CL and CH groups, the expression of p-Akt and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in group P , and the the expression of p-ERK1∕2 and c-fos was up-regulated in group M ( P<0. 05) . Compared with group CH, the MWT was significantly decreased, and the TWL was shortened in P and M groups, the expression of p-ERK1∕2 and c-fos was down-regulated in group P, and the expression of p-Akt and Bcl-2 was down-regulated, and the expression of Bax was up-reg-ulated in group M ( P<0. 05) . Conclusion Curcumin can reduce lidocaine-induced nerve injury, and the mechanism may be partly related to enhancing the activity of Akt and ERK1∕2 signaling pathway in rats.