ABSTRACT
Objective Beta platelet-derived growth factor receptor ( PDGFR-β)-mediated signaling plays a key role in mor-phine tolerance , but its molecular mechanisms are not yet completely understood .The present study aims to investigate whether the ex-tracellular signal-regulated kinase ( ERK) and cyclic AMP response element binding protein ( REB) signaling pathways are involved in the development of PDGFR-βactivation-induced morphine tolerance in rats . Methods Thirty-six adult male SD rats were randomly divided into six groups of equal number:normal saline (20μL), morphine (15μg), morphine +imatinib (morphine 15μg +ima-tinib 10μg), morphine +PDGF-BB (morphine 15μg +PDGF-BB 10 ng), imatinib (10μg), and PDGF-BB (10 ng), all treated intrathecally at 20μL once daily for 7 consecutive days .Paw withdrawal latency ( PWL ) was measured 1 d before and 30 min after medication at 1, 3, 5, and 7 days, respectively, followed by calculation of the maximal possible effect of analgesia (MPE).On the 8th day, PWL was again obtained from all the rats at 30 min after intrathecal injection of morphine (15μg).Then, all the animals were sacrificed and the L4-5 segment of the spinal cord was isolated for determination of the expressions of ERK , phosphorylated ERK ( p-ERK) , CREB, and phosphorylated CREB ( p-CREB) by Western blot. Results At 5 and 7 days after medication, MPE was significant decreased in the morphine group ([52.90 ±8.20] and [15.12 ±3.80] %) and the morphine +PDGF-BB group ([43.51 ±5.42] and [14.81 ±3.60] %) as compared with (100.00 ± 0.00) %in both groups at 1 day (P<0.05), but had no significant changes in the morphine +imatinib group at 1, 3, 5, and 7 days.After intrathecal injection of morphine on the 8th day, MPE was (16.22 ±2.51) %in the morphine group, (15.22 ±3.50) %in the morphine +PDGF-BB group, and (35.21 ±4.51) %in the PDGF-BB group, all remarkably lower than (100.00 ±0.00) %in the control group (P<0.05).There were no significant differences in the expression levels of ERK and CREB among the six groups.The expressions of spinal p-ERK and p-CREB were markedly increased in the morphine , morphine +PDGF-BB, and PDGF-BB groups as compared with the control group (P<0.05), but significantly decreased in the morphine +imatinib group in compari-son with the morphine group, (P<0.05). Conclusion The PDGFR-βsignaling pathway plays an important role in the develop-ment of tolerance to morphine-induced analgesia and its underlying mechanisms may be associated with the activation of the ERK and CREB pathways .
ABSTRACT
Objective To observe the effects of nAChR antagonistα-conotoxin Eb1.6 on ther-mal pain threshold and spinal IL-1βexpression levels and astrocytes activation in rats using L5 spinal nerve transaction (SNT)model.Methods Fifty male Sprague-Dawley rats were randomly assigned into 5 groups with each group 10 rats:sham group,different doses of α-CTX Eb1.6 (0.1 5,1.5 and 1 5 nmol/kg)groups and the saline group after SNT.Saline solution or different doses of Eb1.6 were intraperitoneally injected seven days after the surgery when the model was stable and the treatment continued for seven days.Measured the TWLs of all groups of the rats 1,2,4,7,12 hours after the in-jection on 7 d and 13 d.The rats were sacrificed and L5 spinal cord tissues were collected immediately after the behavioral tests on 13 d.The expression of GFAP and IL-1βwere assessed by Western blot assay and enzyme linked immunosorbent assay (ELISA)separately.Results Groups E1,E2,E3 and C had shorter TWL before the injection on 7 d and 13 d than group N(P <0.05).The TWLs of the rats in groups E1,E2 and E3 of 1 h,2 h and 4 h after the injection on 7 d were significantly higher than that before the injection(P <0.05)with 2 h after the injection showed the most obvious change.The TWL of 1 h,2 h,4 h and 7 h after the injection of the rats in group E1,E2 and E3 and those of 12 h after the injection of the rats in group E2 and E3 on 13 d were significantly higher than that before the injection(P <0.05 )and also higher than TWL of the respective time points on 7 d(P < 0.05 ),also with 2 h after the injection showed the most obvious change.The TWLs of 2 h after the injection a-mong group E1,E2 and E3 showed significant differences both on 7 d and 13 d (P <0.05).Rats spi-nal IL-1βand GFAP expression levels of group E1,E2,E3 and C were significantly higher than those of group N(P <0.05).Rats spinal IL-1β and GFAP expression levels of groups E1,E2,E3 signifi-cantly decreased compared with group C(P <0.05).There were significant differences among the spi-nal IL-1βand GFAP expression levels of group E1,E2 and E3(P <0.05).Conclusion Eb1.6 dose-de-pendently reduced the thermal hyperalgesia induced by L5 spinal nerve transection.Repeated treat-ment of Eb1.6 could produce better analgesic effect,which might be partly attribute to the inhibition of spinal IL-βlevels and astrocytes activation.
ABSTRACT
Combined with the concept and content,forming and adjustment of the theory of psychological contract as well as the impact of the breach of psychological contract,this paper analyzed the impact of psychological contract upon employment work,brought forward that enhancing the management of psychological contract and forming reasonable psychological contract had important meaning to enhance employment quality of university graduates and lessen contact breaks.
ABSTRACT
Combined with the university graduates'employment situation and aiming at employment problems existing in the university,employers and graduates,this paper,based on the concept of competency and combining students cultivation with their career development,puts forward building a management system that harmonizes university's cultivating talents,employers'fetching in graduates and students'making career plan.