Objective To explore the effect of schisanhenol on adipokine expression in 3T3-L1 adipocyte and its related mechanism. Methods 3T3-L1 adipocyte was cultured in vitro and induced to differentiation and maturity. Glucokinase was added to culture medium to make an oxidative model. The expression of adipocytokines were detected under the circumstance of different doses and at different time points of schisanhenol. Results The expression of adiponectin, leptin, resistin and visfatin were decreased with the increase of glucokinase concentration. Concentration-dependent inhibition effect was most obvious in leptin (25 mU/ml Glucokinase vs Blank group, t =7.29, P＜0.01). With pretreatment of oxidative stress, the adipocytokines increased as the doses of schisanhenol increased (t=6.31,P＜0.01 in adiponectin;t=5.92, P＜0.01 in leptin; t=3.77, P＜0.05 in resistin; t=3.63,P＜0.05 in visfatin). With the extension of schisanhenol effect, the expression of four adipokines showed the process of first decrease-then increase'. The effects of schisanhenol on adipokines were parallel with the alteration of oxidative stress. Conclusions Schisanhenol increased adipocytokines expression in 3T3-L1 adipocyte by reducing oxidative stress, and the increase of leptin and adiponectin were most obvious, which indicated that schisanhenol could play a role in the treatment of diabetes by Chinese herb wuweizi.

AIM: To compare the permeation enhancing characters of menthol and azone on the model drug of indomethacin and to study the enhancing effect when the two agents were used in combination. METHODS: The transdermal test was conduced on the penetration experiment apparatus of isolated skin. The cumulate penetrated amount, penetrating rate, stable flux and lag time were calculated upon the concentrations. RESULTS: After adding the penetration enhancer, the penetrating rate of indomethacin increased remarkably. It was 6.21 , 4.91 and 6.92 times of that of the controls respectively. When used in combination, the two penetration enhancers increased much more the penetrating rate than being used separately (P

Objective To establish the method for the content determination of sinomenine in Qiwei Tongbi oral liquid. Methods Sinomenine ofQiwei Tongbi oral liquid was determined by HPLC, with the column being Waters XTerra column temperature setting at 25℃, flow rate being 1.0 ml/min, and the detective wavelength being 262 nm. Results There was a good linearity of sinomenine in the range of 0.248～2.480 μg, and the average recovery was 98.82% with RSD of 0.13%. Conclusion This method was simple, accurate, reproducible, and thus could be used for quality control of Qiwei Tongbi oral liquid.

Objective To evaluate the role of p38 MAPK signal transduction pathway in dexmedetomidine against neurotoxicity induced by bupivacaine.Methods Seventy-two adult male SD rats,successfully implanted with intrathecal catheter without complications,were randomly divided into 6 groups: control group (group C);p38MAPK inhibitor group(group SB);dexmedetomidine group (group D);bupivacaine group (group B);dexmedetomidine and bupivacaine group (group DB);p38MAPK inhibitor and bupivacaine group (group SBB).DMSO 20 μl were injected intrathecally in group C;p38MAPK inhibitor 30 μg and 5% bupivacaine were respectively injected intrathecally in group SB and B;group DB and SBB were respectivel pretreated with dexmedetomidine 75 μg/kg intraperitoneally and p38MAPK inhibitor 30 μg intrathecal injection 20 min before intrathecally injected 5% bupivacaine.Dexmedetomidine 75 μg/kg was injected intraperitoneally in group D.Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured before intrathecal catheter was implanted (T0),before intrathecal administration (T1) and at 4,8 and 12 h and on 1,2,3,4,5 and 6 days after intrathecal administration (T2-T10).At 24 h after intrathecal administration,6 rats were randomly chosen from each group and sacrificed.The lumbar segment (L4-5) of the spinal cord was removed for detecting neuronal apoptosis (by TUNEL) and phosporylated p38MAPK(p-p38MAPK) expression (by Western blot).Results Compared with T0,MWT was significantly increased and TWL was prolonged at T2-T9 in group B,MWT at T2-T7 was significantly increased and TWL at T2-T6 was prolonged in group DB,MWT was significantly increased and TWL was prolonged at T2-T5 in group SBB (P<0.05).Compared with group C,no significant difference was found in MWT,TWL,the apoptotic index and expression of p-p38MAPK in groups D and SB.MWT was significantly increased and TWL was prolonged at T2-T9 in group B,the apoptotic index and expression of p-p38MAPK were significantly increased in group B (P<0.05).Compared with group B,MWT and TWL at T2-T9,the apoptotic index and expression of p-p38MAPK were significantly decreased in groups DB and SBB (P<0.05).Conclusion Dexmedetomidine can inhibit spinal neurotoxicity induced by bupivacaine in rats via inhibiting apoptosis in spinal cord,and inhibition of p38 MAPK signal transduction pathway may be involved in the underlying mechanism.

Aim To investigate the protective effects of Diterpene Ginkgolides Meglumine Injection(DGMI)on SY5 Y cells damaged by oxygen-glucose deprivation and its functional mechanisms.Methods After 4 h of OGD,the cells were treated with 25 mg·L-1 drugs for 1 h.Subsequently,cell viabilities were measured by cell counting kit-8(CCK-8 kit)and cell apoptosis was measured by flow cytometric analysis.Furthermore, the mitochondrial membrane potential was detected by rhodamine123 staining.The levels of phospho-p38, phospho-p53,Bcl-2,Bax and cleaved caspase-9/3 were evaluated by western blot.Results DGMI signif-icantly increased the cell viabilities of SY5 Y cells dam-aged by OGD,and reduced OGD-elicited dissipation of mitochondrial membrane potential and cell apoptosis. Furthermore,DGMI also reduced p-p38,p-p53,Bax/Bcl-2 ratio,cleaved caspase-9 and cleaved caspase-3. Conclusion DGMI shows good neuroprotective effects on SY5 Y cells after oxygen-glucose deprivation.The underlying mechanisms may be associated with the sup-pression of p38/p53/Bcl-2 /caspase-9/caspase-3 sig-naling pathway.

OBJECTIVE To investigate the protective effects and mechanism of diterpene ginkgolides meglumine injection (DGMI) against oxidative stress induced by oxygen-glucose deprivation (OGD) in SH-SY5Y cells. METHODS SH-SY5Y cells were divided into five groups: normal control, model control (OGD group) and drug(25 mg · L- 1) administration groups including DGMI group, extract of ginkgo biloba leaves injection group (EGBLI) and lactones ginkgo biloba injection group (LGBI). The cells suffered from oxygen-glucose deprivation (OGD) for 4 h, followed by reoxygenation with drugs for 6 h. Then, cell viabilities were detect using CCK-8 assays, reactive oxygen species (ROS) levels using fluorescence probe DCFH-DA and superoxide dismutase (SOD) activities using WST-1 test. Western blotting was used to detected protein levels of hemeoxygenase-1(HO-1), NAD(P)H, quinone oxidore?ductase l (Nqo1), protein kinase B (Akt), phosphorylated Akt (p-Akt), nuclear factor-E2-related factor2 (Nrf2) and phosphorylated Nrf2 (p-Nrf2). The cells were induced by OGD for 4 h, followed by reoxygen?ation and DGMI for 1 h, combined with different concentrations of PI3K inhibitor (LY294002) (at the final concentration of 12.5, 25 and 50 μmol · L-1) before the protein levels of AKT, p-AKT, Nrf2 and p-Nrf2 were detected by Western blotting. RESULTS SH-SY5Y cells induced by OGD for 4 h resulted in an increase in ROS(P<0.01), but a decrease in cell viabilities(P<0.01), SOD activities(P<0.01), and antioxidant protein levels ( Akt, p-Akt, Nrf2, p-Nrf2, HO-1 and Nqo1) (P<0.01). Compared with OGD group, treatment with reoxygenation and drugs (DGMI,EGBLI and LGBI respectively) for 6 h resulted in a decrease in ROS (P<0.01), but an increase in cell viabilities, SOD activities and antioxidant protein levels of p-Nrf2, HO-1, Nqo1 and p-Akt(P<0.05,P<0.01). DGMI group showed the best efficiently. Moreover, after OGD for 4 h, compared with DGMI group, combining reoxygenation and DGMI with LY294002 for 1 h resulted in a concentration-dependent inhibition of the protein levels of p-AKT and p-Nrf2(P<0.01). CONCLUSION DGMI 25 mg · L-1 can inhibit oxidative stress in SH-SY5Y cells induced by OGD by increasing the activity and expression of Nrf2 through PI3K/Akt pathway, which may be one of the mechanisms by which DGMI protects neurons from stroke.

Objective To evaluate the role of C-Jun N-Terminal kinase (JNK) signaling pathway in dexmedetomidine-induced reduction of spinal neurotoxicity induced by lidocaine in rats.Methods Seventy-two adult male Sprague-Dawley rats, weighing 280-320 g, in which intrathecal catheters were successfully implanted without complications, were randomly divided into 6 groups (n =12 each) using a random number table: control group (group C);SP600125 (JNK signaling pathway blocker) group (group SP);dexmedetomidine group (group D);lidocaine group (group L);dexmedetomidine + lidocaine group (group DL);SP600125+lidocaine group (group SPL).Dimethyl sulfoxide (DMSO) 20 μl was injected intrathecally in group C.SP600125 30 μg and 10％ lidocaine 20 μl were injected intrathecally in SP and L groups, respectively.At 20 min after intrathecal injection of 10％ lidocaine, dexmedetomidine 75 μg/kg was injected intraperitoneally in group DL, and SP600125 30 μg was injected intrathecally in group SPL.Dexmedetomidine 75 μg/kg was injected intraperitoneally in group D.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before intrathecal catheters were implanted (T0), before intrathecal administration (T1), and at 4, 8 and 12 h and 1, 2, 3, 4, 5 and 6 days after intrathecal administration (T2-10).At 24 h after intrathecal administration, 6 rats randomly selected from each group were sacrificed.The lumbar segment (L4-5) of the spinal cord was removed for detection of cell apoptosis (by TUNEL) and phosphorylated JNK (p-JNK) expression (by Western blot).The apoptotic index was calculated.Results Compared with group C, no significant change was found in the MWT, TWL, apoptotic index and expression of p-JNK in SP and D groups (P＞0.05), the MWT at T2-8 in group L, at T2-6 in group DL and at T2-5 in group SPL were significantly increased, the TWL at T2-8 in group L, at T2-5 in group DL and at T2-4 in group SPL were prolonged, and the apoptotic index and expression of p-JNK were increased in DL, SPL and L groups (P＜0.05).Compared with group L, the MWT was significantly decreased, and the TWL was shortened at T2-8, and the apoptotic index and expression of p-JNK were decreased in DL and SPL groups (P＜0.05).Conclusion The mechanism by which dexmedetomidine mitigates spinal neurotoxicity induced by lidocaine is related to inhibited activation of JNK signaling pathway in rats.

Objective To investigate the effect of intrathecal hyperbaric bupivacaine on spinal cord neurons apoptosis in diabetic neuropathic rats.Methods Thirty-two healthy male Sprague-Daw-ley rats weighing 220-300 g,8 normal rats randomly served as control group (group C),the other rats were intraperitoneal injection 1% streptozotocin (STZ)60 mg/kg to induce diabetic neuropathic (DN),and last induced thirty-seven diabetic neuropathic rats.group C and diabetic neuropathic rats administer intrathecal catheter,respectively.Twenty-four rats in which DN was successfully intrathe-cal catheter were randomly divided into 3 groups (n=8):hyperbaric bupivacaine group (group HB), isobaric bupivacaine group (group IB),glucose group (group G).Hyperbaric bupivacaine 10 μl were injected intrathecally in groups C and HB respectively,isobaric lidocaine 10 μl were injected intrathe-cally in group IB,10% glucose 10 μl were injected intrathecally in group G,once daily for 3d.After rats each administration 2 min,motor block duration were recorded;The paw withdrawal threshold to von Frey filament stimulation (PWT)were measured before induced diabetes model (T1 ),before in-jected intrathecally (T2 ),after 30 min administered 1 d (T3 ),2 d (T4 ),3 d (T5 )and end administered 4 d (T6 ).All rats were sacrificed at T6 and their lumbar intumescential spinal cord tissue were re-moved for microscopic examination.And using TUNEL assay to measure spinal neuronal apoptosis. Results PWT was lower at T2-5 in groups HB,IB and G comparing with T1 (P <0.05 ).Comparing with group C,the motor block duration was significantly prolonged(P <0.05)and spinal cord neuro-nal apoptosis cells were increased(P <0.05)in group HB.Comparing with group IB,the motor block duration was significantly prolonged(P <0.05)and spinal cord neuronal apoptosis cells were increased (P <0.05)in group HB,too.PWT was increased at T6 in group HB at T2-T5 (P <0.05).Group G did not appear motor block and spinal cord neuronal apoptosis.Conclusion Intrathecally hyperbaric bupi-vacaine can promote spinal cord neuronal apoptosis in diabetic neuropathic rats.

Objective To discuss the effects and related mechanisms of rapamycin preconditioning on lung injury induced by limb ischemia-reperfusion (IR) in rats.Methods Sixty healthy male SD rats, aged 4-5 months, weighing 250-300 g, were randomly divided into 5 groups (n=12 each) using a random number table: sham operation group (group S);limb ischemia-reperfusion group (group IR);rapamycin 1, 5, 10 mg/kg pretreatment groups (groups R1, R5 and R10).Ischemia-reperfusion of limb was produced by occlusion of bilateral femoral arteries for 2 h followed by 3 h reperfusion.Blood samples were collected to determine serum superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations,1ungs were removed for microscopic examination and for determination of wet/dry lung weight ratio.Results The activity of SOD in groups IR, R1 and R5 was significantly lower than that in group S (P＜0.05).The activity of SOD in groups R1, R5 and R10 was significantly higher than that in group IR, that in groups R5 and R10 was significantly higher than that in group R1, that in group R10 was significantly higher than that in the group R5 (P＜0.05).Serum MDA, IL-1β, IL-6, TNF-α concentrations and wet/dry lung weight ratio were significantly increased in groups IR, R1 and R5 (P＜0.05).Serum MDA, IL-1β, IL-6,TNF-α concentrations and wet/dry lung weight ratio were lower in groups R1, R5 and R10, those in groups R5 and R10 were significantly lower than those in group R1, those in group R10 was significantly lower than those in group R5 (P＜0.05).Compared with group S, the lung tissue injured more significantly in group IR.Compared with group IR, the lung tissue injury gradually reduced in groups R1,R5 and R10.Conclusion Rapamycin pretreatment can reduce lung injury caused by limb ischemia-reperfusion injury in rats in a dose-dependent manner, the greater the dose, the stronger the effect of reducing lung injury caused by limb ischemia-reperfusion injury.The mechanisms may involve attenuating oxidative stress and inhibiting inflammatory response.

Aim To investigate the protective effects of YXETNZ injection on SH-SY5 Y cells damaged by oxygen-glucose deprivation ( OGD ) , and explore its functional mechanisms. Methods After 4 h of OGD, the cells were treated with 25 mg·L-1 drugs for 1 h. Subsequently, cell viabilities were measured by cell counting kit-8 ( CCK-8 kit ) and cell apoptosis was measured by caspase-3/7 assay kit according to manu-facturer’ s instructions. Furthermore, cell death was also detected by ELISA. The levels of phospho-Akt, phospho-PKA,phospho-Bad were evaluated by western blot. Results Oxygen-glucose deprivation significant-ly decreased the cell viabilities of SH-SY5Y cells, while YXETNZ injection significantly increased cell vi-abilities, phospho-Akt, phospho-PKA and phospho-Bad. Furthermore, YXETNZ injection also reduced the activities of caspase-3/7 and cytoplasmic histone-asso-ciated-DNA-fragments contents. Conclusion Our re-searches demonstrat that YXETNZ injection shows good neuroprotective effects on SH-SY5 Y cells after oxygen-glucose deprivation. The underlying mechanisms may be associated with activation of PI3 K/Akt/Bad/caspase-3/7 , cAMP/PKA/Bad/caspase-3/7 signaling pathway.