RESUMEN
Objective To explore the pharmacokinetic changes of single dose of fentanyl in rats in a simulated high-altitude and contributing factors.Methods Thirty-six healthy female SD rats(6～8 weeks old,250±20 g)were randomly divided into high-altitude-acute-exposure group(group A),high-altitude-chronic-exposure group(group S)and control group(group C)through random number table,with 12 rats in each group.The group A and S were housed in a low-pressure chamber simulating the high altitude of 5000 m above sea level for 3 and 30 d respectively,and the group C was housed out of the chamber(at an altitude of 300 m).A single dose of fentanyl was administered through the femoral vein to 6 rats randomly selected from each group.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was used to detect blood concentrations of fentanyl and WinNonlin 8.2 software was used to calculate the pharmacokinetic parameters,while blood samples were taken through the femoral artery before and in 1,2,4,8,15,30,60,120 and 180 min after administration.The remaining 6 rats were ultrasonographically assessed for portal vein internal diameter(PVD),peak flow velocity(PVV)and blood flow(PVF),and liver tissues were collected for CYP3A1 protein content assay.Results The blood drug concentrations of fentanyl in the group A and group S were significantly lower than those in the group C at 60,120,and 180 min(P=0.002,P＜0.001,P= 0.001).Compared with the group C,the clearance rate(CL)of the group A was increased by 54.06%(P=0.021),and the mean residence time(MRTlast)was shortened by 24.21%(P=0.033);CL of the group S was increased by 50.10%(P=0.041),the area under the concentration-time curve(AUC0-t,AUC0-∞)and MRTlast were reduced by 18.92%(P=0.039),27.54%(P=0.018)and 33.61%(P= 0.004),respectively.PVD and PVF in the group S increased by 10.87%(P=0.006)and 42.50%(P= 0.006)when compared with the group C.The CYP3A1 protein content in the group A was 28.74%,which was higher than that in the group C(P=0.048).Conclusion Fentanyl is cleared significantly faster after a single dose in rats in simulated high-altitude,which may be related to the increased liver blood flow and increased CYP3A1 protein expression in liver.
RESUMEN
Objective To observe the expression of pannexin1(PX1) in the dorsal horn of spinal cord in model ratwith neu-ropathipain afteselective ligation of sciatinerve branche.Method50 male SD ratwere randomly divided into 3 group,inclu-ding the control group(Wgroup ,n= 10) ,sham operation group(sham group ,n= 10) and sciatinerve branch selective injury group(SNI group ,n=30) .30 ratwere killed on postoperative 3 ,5 ,7 ,14 d and the lumbasegmenof the spinal cord wataken fodetecting the expression of PX1 by using Western blo.Othe20 ratwere killed on 7 d afteSNI and the expression of glial fibril-lary acidiprotein(GFAP) in the spinal cord wadetected with immunohistology .Among them ,10 ratin the SNI group were trea-ted with intrathecal intubation before operation and administrated with saline 20 μL ocarbenoxolone(CBX) 20 μL by intrathecal injection on postoperative 7 d fodetermining the expression of GFAP by the immunohistology .ResultThe expression of PX1 in the SNI group waincreased and enhanced with time ,which wasignificantly highethan thain the Wgroup and the sham group (P＜0 .05);the GFAP expression on 7 d in the SNI group waobviously increased compared with the Wgroup and the sham group(P＜0 .05);afteintrathecal injection of CBX ,the expression of GFAP wasignificantly decreased compared with thain the normal saline group(P＜0 .05) .No statistically significandifferencein the expression of PX1 and GFAP were found in the Wgroup and the sham group .Conclusion PX1 may be involved in the activation of astrocyte,prompting thaPX1 playan importanrole in the neuropathipain caused by the peripheral nervel injury .
