Effect of microRNA-217 on pain behavior and neuro-inflammatory factors in rats with partial sciatic nerve ligation / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To observe the effect of microRNA-217 (miR-217) on neuropathic pain and neuro-inflammation in rats with partial sciatic nerve ligation (pSNL).Methods:Twenty-four healthy adult male SD rats were randomly divided into three groups pSNL group (partial sciatic nerve ligation), Sham group (Sham surgery), and normal group (no treatment) with 8 in each group. The mechanical withdrawal threshold (MWT) and paw withdrawal thermal latency (PWTL) were measured on the 1st, 2nd and 3rd day before surgery and on the 1st, 3rd, 7th and 14th day after surgery.The mRNA expression changes of miR-217 and TLR5 in the spinal cord of rats were detected by qRT-PCR. Additionally, 24 healthy adult male SD rats were randomly divided into three groups pSNL- LV-miR-217 group (sciatic nerve part ligation + intrathecal injection of LV-miR-217), pSNL- LV-NC group (sciatic nerve part ligation + intrathecal injection of LV-NC), and Sham operation group with 8 in each group. MWT and PWTL were measured on the first, second and third day before surgery and on the 1st, 3rd, 7th, 14th day after surgery.Results:The results of pain behavior showed that the MWT of SNL group decreased significantly on the 7th day ((6.72±0.15) g, t=11.79, P<0.05) and the 14th day ((5.72±0.22) g, t=17.83, P<0.05), compared with sham group (7th d (13.58±0.30) g, 14th d (14.54±0.51)g). PWTL of pSNL group was (6.78±0.21) s and (5.99±0.22)s respectively on the 7th and 14th day after operation, which was lower than those of Sham group ((14.86±0.35) s, (14.50±0.51) s), the difference was statistically significant ( t=4.86, 7.13, both P<0.05). The qPCR experiment showed that the expression of miR-217 was down-regulated and the expression of TLR5 was up-regulated in the spinal cord of rats in the pSNL group, showing significant differences compared with the Sham group ( t=8.94, P<0.01; t= 7.54, P<0.01). The MWT of the pSNL- LV-miR-217 group were significantly increased on the 7th and 14th day after the intraoperative injection of miR-217, showing a significant difference compared with the pSNL-LV-NC group (7th d t=14.79, P<0.01; 14th d t=15.83, P<0.01). The PWTL of the pSNL-LV-miR-217 group were significantly increased(7th d t=14.95, P<0.01; 14th d t=16.27, P<0.01). qPCR assay showed that compared with the pSNL-LV-NC group, the expression of miR-217 in the pSNL-LV-miR-217 group was significantly increased ( t=7.49, P<0.01), and the expression of TLR5, COX-2( t=8.82, P<0.05), IL-6( t=6.42, P<0.05) and TNF-α( t=7.46, P<0.05) was significantly decreased. Western blot assay showed that the protein expressions of TLR5, COX-2, IL-6 and TNF-α in pSNL-LV-miR-217 group were significantly decreased on the 7th day after the operation. Conclusions:Intrathecal injection of miR-217 can significantly alleviate sciatic nerve ligation neuropathic pain and may inhibit neuroinflammation by regulating TLR5.