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Objective To evaluate the role of spinal cord tumor necrosis factor receptor-associated factor 6 (TRAF6)/nuclear factor kappa B (NF-κB)signaling pathway in the development of diabetic neuropathic pain (DNP)in rats.Methods Clean-grade healthy adult male Sprague-Dawley rats,aged 2 months,weighing 180-230 g,in which IT catheters were implanted,were used in this study.Streptozotocin 60 mg/kg was intraperitoneally injected after IT catheterization to establish the model of DNP.Twelve DNP rats were divided into 2 groups (n =6 each) by a random number table method:DNP group and DNP plus TRAF6 inhibitor group (group DTR).Another 6 age-matched Sprague-Dawley rats were used as normal control group (group NC).The rats in group DC and group DTR received IT injection of dimethyl sulfoxide 10 μl and TRAF6 inhibition 10 μg,respectively,once a day for 7 consecutive days starting from day 21 after establishing the model.The mechanical paw withdrawal threshold (MWT) was determined before establishing the model (T1),on 7,14 and 21 days after establishing the model (T2-4),and on 1,4 and 7 days after IT injection (T5-7).The rats were sacrificed after the last MWT measurement,and the L3-5 segments of the spinal cord were removed for determination of the expression of TRAF6 and NFκB p65 by Western blot.Results Compared with group NC,the MWT at T3-7 in group DC and at T3-6 in group DTR was significantly decreased,and the expression of spinal TRAF6 and NF-κB p65 was up-regulated in DC and DTR groups (P＜0.05).Compared with group DC,the MWT was significantly increased at T6-7,and the expression of spinal TRAF6 and NF-κB p65 was down-regulated in group DTR (P ＜ 0.05).Conclusion Spinal cord TRAF6/NF-κB signaling pathway is involved in the development of DNP in rats.
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Objective To observe the protective effect of dexmedetomidine(Dex)at different doses com-bined with ulinastatin in lung resection patients with one lung ventilation. Methods 80 patients having undergone unilateral lung resection were divided into four groups randomly:control group(C group)and groups Dex 1-3,20 cases in each group.One lung ventilation(OLV)was used in all the groups during operation.The patients in groups Dex 1-3 were treated with 0.5,1.0,2.0 μg/kg combined with ulinastatin,and the C group with amount of normal sa-line instead.The comparisons were done among the four groups in terms of SOD,L-6,IL-10,serum malondialde-hyde(MDA)concentration at 5 min after endotracheal intubation(T0),30 min(T1),60 min(T2),120 min (T3)as well as the levels of FVC,FEVl and FEVl/FVC at 24 h,48 h and 72 h after surgery. Results In the groups C and Dex 1,SOD decreased at T1-4 and IL-6,MDA and IL-10 at T2-4 rose.SOD decreased at T2-4 in groups Dex 2-3 and MDA,IL-6 and IL-10 rose.Compared with group C,the levels of SOD and IL-10 at T2-4 in groups Dex 1-2 and at T1-4 in group Dex 3 rose. In groups Dex 1-3,postoperative FVC,FEVl and FEVl/FVC rose.Compared with group Dex 1 or 2 respectively,SOD and IL-10 at T2-4 in group Dex 3 significantly rose,but MDA and IL-6 significantly declined;FVC,FEVl and FEVl/FVC significantly rose 48 h and 72 h after surgery (P<0.05). Conclusion Dex combined with ulinastatin has a protective effect for patients with one lung ventila-tion after lung resection,with the best-suggested dose of 1.0 μg/kg.
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Objective To evaluate the effect of resveratrol on the activity of NADPH oxidase during acute lung injury induced by intestinal ischemia-reperfusion (I/R) in rats.Methods Thirty-two pathogenfree healthy female Sprague-Dawley rats,weighing 180-230 g,were divided into 4 groups (n =8 each) using a random number table:sham operation group (Sham group),intestinal I/R group (I/R group),vehicle group (Veh group) and resveratrol group (Res group).Intestinal I/R was produced by occlusion of the superior mesenteric artery for 75 min followed by 4 h of reperfusion.In group Res,resveratrol 15 mg/kg was intraperitoneally injected for 5 consecutive days before establishment of the model and at 15 min before ischemia.The equal volume of vehicle (0.5％ alcohol) was intraperitoneally injected in group Veh.The equal volume of normal saline was intraperitoneally injected in Sham and I/R groups.At the end of reperfusion,the rats were sacrificed and the lung was removed for microscopic examination of pathologic changes which were scored and for determination of wet/dry weight ratio (W/D ratio),malondialdehyde (MDA) content and superoxide dismutase (SOD) activity (by colorimetric method) and expression of NADPH oxidase subunits (gp91phox and p47phox) in lung tissues (by Western blot).Results Compared with group Sham,pathologic scores,W/D ratio and MDA content were significantly increased,the expression of gp91phox and p47phox was up-regulated,and the activity of SOD was decreased in I/R and Veh groups (P＜0.05).Compared with I/R and Veh groups,pathologic scores,W/D ratio and MDA content were significantly decreased,the expression of gp91phox and p47phox was down-regulated,and the activity of SOD was increased in group Res (P＜0.05).Conclusion The mechanism by which resveratrol reduces intestinal I/R-induced acute lung injury is related to inhibiting NADPH oxidase-mediated oxidative stress response of rats.
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Objective To evaluate the effects of curcumin pretreatment on the activity of inducible nitric oxide synthase (iNOS) during lung injury induced by intestinal ischemia-reperfusion (Ⅰ/R) in rats.Methods Twenty-four pathogen-free female Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups (n =8 each) using a random number table:sham operation group (group Sham);intestinal Ⅰ/R group (group Ⅱ/R);curcumin pretreatment group (group Cur).A rat model of lung injury induced by intestinal Ⅰ/R which was produced by occlusion of superior mesenteric artery for 75 min followed by reperfusion was established.At 5 days before Ⅰ/R,curcumin 200 mg/kg (in 20 mg/ml of normal saline) was given through a gastric tube in group Cur,while the equal volume of normal saline was given instead in Sham and Ⅱ/R groups.The rats were sacrificed at 4 h of reperfusion,and the pulmonary specimens were obtained for determination of wet/dry lung weight ratio (W/D ratio),NO content (by using nitrate reductase method) and iNOS activity (using colorimetric method) and for examination of pathological changes (with light microscope).The pathological changes of the lung were scored.Results Compared with group Sham,the pathological scores,W/D ratio,NO content and iNOS activity were significantly increased in Ⅱ/ R and Cur groups.Compared with Ⅱ/R group,the pathological scores,W/D ratio,NO content and iNOS activity were significantly decreased in group Cur.The pathological changes of lungs were significantly attenuated in group Cur as compared with H/R group.Conclusion The mechanism by which curcumin pretreatment attenuates lung injury induced by intestinal Ⅰ/R is related to decrease in iNOS activity in rats.
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Objective To evaluate the effect of curcumin preconditioning on the activation of mast cells during intestinal ischemia/reperfusion (I/R) in rats.Methods Twenty-four female Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups (n =8 each) using a random number table:sham operation group (S group),intestinal I/R group (I/R group),and curcumin preconditioning group (Cur group).Intestinal I/R was produced by occlusion of superior mesenteric artery (SMA) for 75 min followed by reperfusion.At 5 days before I/ R,curcumin 200 mg/kg (in 20 mg/ml normal saline) was given through a gastric tube in Cur group,while the equal volume of normal saline was given instead in S and I/R groups.All the rats were sacrificed at 4 h of reperfusion,and the intestinal specimens were obtained for microscopic examination and for determination of tryptase expression and β-hexosaminidase content.Intestinal damage was assessed and scored according to Chiu.Results Compared with S group,Chiu's score and β-hexosaminidase content were significantly increased,and the expression of tryptase was up-regulated in I/R and Cur groups.Compared with I/R group,Chiu' s score and β-hexosaminidase content were significantly decreased,and the expression of tryptase was down-regulated in Cur group.Conclusion The mechanism by which curcumin preconditioning attenuates intestinal I/R injury is related to inhibited activation of mast cells of rats.
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Objective To evaluate the effects of curcumin preconditioning on the activity of xanthine oxidase (XOD) during intestinal ischemia-reperfusion (I/R) in rats.Methods Thirty female Sprague-Dawley rats,aged 180-220 g,were randomly divided into 3 groups (n =10 each) using a random number table:sham operation group (S group),intestinal I/R group (I/R group),and curcumin preconditioning group (Cur group).Intestinal I/R was induced by clamping the superior mesenteric artery for 75 min followed by reperfusion.Curcumin 200 mg/kg was given everyday for 5 days before intestinal I/R in Cur group and the equal volume of normal saline was given instead of curcumin in S and I/R groups.The rats were sacrificed at 4 h of reperfusion and the intestinal specimens were obtained for microscopic examination of pathologic changes which were graded using Chiu scoring system and for determination of XOD activity,content of malondialdehyde (MDA),and superoxide dismutase (SOD) activity.Results Compared with S group,the Chiu score,activity of XOD and content of MDA were significantly increased,while the activity of SOD was decreased in I/R and Cur groups (P ＜ 0.05).Compared with I/R group,the Chiu score,activity of XOD and content of MDA were significantly decreased,and the activity of SOD was increased in Cur group (P ＜ 0.05).Conclusion Curcumin preconditioning can attenuate intestinal I/R injury in rats,which may be due to inhibition of XOD activity and decreased oxidative stress in intestinal tissues.
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Objective To evaluate the effect of intrathecal rapamycin on diabetic neuropathic pain in rats.Methods Thirty adult male Sprague-Dawley rats,weighing 180-220 g,in which IT catheters were successfully implanted,were randomly divided into 5 groups (n =6 each) using a random number table:control group (group C),diabetic neuropathic pain group (group DN),rapamycin 1 μg group (group R1),rapamycin 3 μg group (group R3) and rapamycin 10 μg (group R10).Diabetes mellitus was induced by intraperitoneal streptozotocin (STZ) 60 mg/kg on 5 days after IT catheters were implanted in DN,R1,R3 and R10 groups.Citric acid-sodium citrate buffer 6 ml/kg was injected intraperitoneally in group C.In R1,R3 and R10 groups,rapamycin (dissolved in 10 μl 4％ dimethyl sulfoxide) 1,3 and 10 μg were intrathecally injected,respectively,once a day for 7 consecutive days starting from day 21 after STZ injection,while the equal volume of 4％ dimethyl sulfoxide was given instead in C and DN groups.Paw withdrawal threshold (PWT) to yon Frey filament stimulation was measured before IT catheters were implanted,before STZ injection,on 7,14 and 21 days after STZ injection,and on 1,3,5 and 7 days after rapamycin administration.After measurement of PWT,the rats were sacrificed and L2-5 segments of the spinal cord were removed for determination of the expression of mTOR and phosphorylated mTOR (p-mTOR),S6K and phosphorylated S6K (p-S6K) (by Western blot) and expression of mTOR mRNA and S6K mRNA (by RT-PCR).Results Compared with group C,MWT was significantly decreased at 14 and 21 days after STZ injection in DN,R1,R3 and R10 groups,and the expression of mTOR,p-mTOR,S6K,p-S6K,mTOR mRNA and S6K mRNA was up-regulated in group DN (P ＜ 0.01).Compared with group DN,MWT was significantly increased at 5 and 7 days after rapamycin administration in group R1,at 3,5 and 7 days after rapamycin administration in group R3,and at 1,3,5 and 7 days after rapamycin administration in group R10,and the expression of mTOR,p-mTOR,S6K,p-S6K,mTOR mRNA and S6K mRNA was down-regulated in R1,R3 and R10 groups (P ＜ 0.01).Conclusion Intrathecal rapamycin can alleviate diabetic neuropathic pain in rats.
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Objective To evaluate the effect of curcumin on spinal inflammatory factor in rats with diabetic neuropathy. Methods Diabetic neuropathy was induced by intraperitoneal injection with 1% STZ (60 mg/kg) in sprague-dawley rats. These diabetic rats were randomly allocated to diabetic group (D group, n=10) and curcumin group ( C group , n = 10 ) . Another 10 age-matched normal rats served as controlled group ( N group , n = 10 ) . 28 days after STZ injection, the rats in C group received daily intragastric administration of curcumin (200 mg/kg) whereas those in D group received the same volume of normal saline for 2 weeks. Caudal vein blood glucose levels at T1( before STZ injection)and at T2-T8(2、7、14、21、28、35、42 days after STZ injection)from all rats were detected. Responses to the mechanical stimulus were measured with von Frey filament, and paw withdraw threshold (PWT) was recorded at T1 and at T3 to T8. At T8,the rats were killed and lumbar segments of spinal cord were removed to detect TNF-αand IL-6 content. Results Compared to N group, rats in both C and D group showed hyperglycemia at T2 to T8 (P<0.05) and lower PWT at T4~ 8 (P < 0.01). Compared to D group, C group showed higher PWT at T7,8(P<0.05). Both D and C group showed higher levels of blood sugar at T2 ~ 8 than that at T1 (P < 0.05). C group showed higher PWT at T7,8 than that at T6(P<0.05). Compared to N group,spinal TNF-αand IL-6 content increased in both D and C groups (P<0.05). Compared to D group, C group had reduction of TNF-αand IL-6 concentration (P < 0.05). Conclusion Curcumin can attenuate diabetic neuropathic pain on rats probably by reducing inflammatory factor in spinal cord.
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<p><b>OBJECTIVE</b>To observe the change of neuronal nitric oxide synthase (nNOS) expression in the spinal cord of diabetic rats with painful diabetic neuropathy.</p><p><b>METHODS</b>Sixty SD rats were randomized equally into painful diabetic neuropathy group (DM group) and control group. Painful diabetic neuropathy was induced by intraperitoneal injection with STZ (60 mg/kg) in DM group, and the rats in the control group received a solvent injection. Blood glucose levels were measured before and at 2, 7, 14, 21, and 28 days after STZ injection (T1-6 respectively). Responses to the mechanical stimulus were measured with von Frey filament, and 50% paw withdraw threshold (PWT) and body weight were recorded at T1 and T3-6. At T1 and T3-6, 6 rats from each group were sacrificed to examine the expression of nNOS in the lumbar segments of the spinal cord using Western blotting.</p><p><b>RESULTS</b>The level of blood glucose increased while the body weight decreased significantly after STZ injection in DM group (P<0.05). Comparing to those in the control group, PWT decreased while spinal nNOS expression increased significantly in DM group at T4-6 (P<0.05) showing an inverse correlation between them (P<0.01).</p><p><b>CONCLUSION</b>The enhanced expression of spinal nNOS might be involved in the pathogenesis of painful diabetic neuropathy in rats.</p>
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Animals , Rats , Blood Glucose , Diabetes Mellitus, Experimental , Diabetic Neuropathies , Nitric Oxide Synthase Type I , Metabolism , Rats, Sprague-Dawley , Spinal CordABSTRACT
Objective To evaluate the role of mTOR in spinal cord in the development of diabetic neuropathic pain in rats.Methods Sixty adult male Sprague-Dawley rats,aged 2 months,weighing 180-220 g,were used in the study.Forty-five rats among them were chosen randomly and diabetes mellitus was induced by intraperitoneal streptozotocin (STZ) 60 mg/kg and confirmed by blood glucose ＞ 16.7 mmol/L on day 3 after STZ injection.The left 15 rats received intraperitoneal injection of the equal volume of citric acid-sodium citrate buffer and served as normal control group (group C).Paw withdrawal threshold to von Frey filament stimulation was measured in the right hind paw before STZ injection and on 3,6,9,12,15,18,and 21 days after STZ injection.The diabetic rats with mechanical pain threshold decreasing by more than 50％ of the baseline were allocated to diabetic neuropathic pain group (group DP),and by less than 25 ％ of the baseline were allocated to diabetic non-neuropathic pain group (group NP).The rats were sacrificed at 21 days after STZ injection,and their lumbar enlargements of the spinal cord were removed for determination of the expression of mTOR and phosphorylated mTOR (p-mTOR) by Western blot.Results The expression of mTOR was significantly up-regulated in DP and NP groups when compared with group C (P ＜ 0.05),the expression of p-mTOR was up-regulated in DP group,and no significant change was found in the expression of p-mTOR in group NP (P ＞ 0.05).Compared with group NP,the expression of p-mTOR was significantly up-regulated (P ＜ 0.05),and no significant change was found in the expression of mTOR in group DP (P ＞ 0.05).Conclusion Activation of mTOR in the spinal cord is involved in the development of diabetic neuropathic pain in rats.
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Objective To evaluate the role of nitric oxide (NO) in the spinal cord in the maintenance of diabetic neuropathic pain in rats.Methods Male Sprague-Dawley rats,aged 2 months,weighing 180-200 g,were used in the study.Diabetes mellitus was induced by intraperitoneal streptozotocin (STZ) 60 mg/kg and confirmed by blood glucose ＞ 16.7 mmol/L on day 2 after STZ injection.Twenty diabetic rats were randomly allocated into diabetes mellitus group (DM group,n =10) and L-NAME (non-selective NOS inhibitor) group (LN group,n =10).Another 10 age-matched normal rats served as control group (C group).On 21 days after STZ injection,L-NAME 10 mg/kg was injected intraperitoneally once a day for 7 consecutive days in LN group,whereas the equal volume of normal saline 5 ml/kg was given instead of L-NAME in DM group.Paw withdrawal threshold to yon Frey filament stimulation (PWT) was measured before STZ infection and on 7,14,21 and28 days after STZ injection.The rats were sacrificed after the last measurement of PWT and the lumbar segments of spinal cord were removed for determination of NO content and neuronal nitric oxide synthase (nNOS) expression (by Western blot analysis) in spinal cord tissues.Results Compared with C group,PWT was significantly decreased on 14,21 and 28 days after STZ injection,and the NO content and nNOS expression in spinal cord tissues were increased in DM and LN groups (P ＜ 0.05).Compared with DM group,PWT was significantly increased on 28 days after STZ injection,and the NO content and nNOS expression in spinal cord tissues were decreased in LN group (P ＜ 0.05).Conclusion NO in the spinal cord is involved in the maintenance of diabetic neuropathic pain in rats and the mechanism is related to the enhanced function of nNOS.
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The effects of various soluble extracts of Ascaris suum on human blood coagulation were studied. The extract of whole worm could prolong recalcification time (RT) and kaolin-activated, partial thromboplastin time (KPTT), but did not alter prothrombin time (PT), indicating that the intrinsic pathway of blood coagulation was inhibited by this extract, but the extrinsic pathway was not affected. Whole worm extract inhibited platelet aggregation induced by ADP, but did not influence the one induced by adrenaline. Neither whole worm extract nor body fluid caused fibrinolysis. In KPTT assays with three dif-ferent extracts, cuticle extract exhibited the strongest anticoagulant activity, while whole worm extract and body fluid much less so. These data suggested that anticoagulants of ascaris mainly exist in the cuticle,