Diabetic neuropathy is a disorder which affects various regions of the nervous sys-tem and there is no specific treatment available for it.So,the present study eval-uated protective effect of molsidomine in diabetic n...Diabetic neuropathy is a disorder which affects various regions of the nervous sys-tem and there is no specific treatment available for it.So,the present study eval-uated protective effect of molsidomine in diabetic neuropathy in rats.Diabetes was induced in male Wistar rats by administrating streptozotocin(52 mg/kg i.p).Diabetic rats were administered with molsidomine 5 mg/kg p.o,and 10mg/kg p.o.as treatment.After 8 weeks of treatment,Motor coordination,Mechanical allodynia,Mechanical hyperalgesia,Nerve conduction velocity,Glycosylated hemoglobin were assessed.Thereafter animals were sacrificed and sciatic nerve was isolated.It was used for reduced glutathione,lipid peroxidation and for histopathology.Treatment with molsidomine significantly improved motor coordination,paw withdrawal threshold,mechanical threshold and nerve conduction velocity.Furthermore,mol-sidomine treatment also reduced malondialdehyde levels and prevented depletion of reduced glutathione in sciatic nerve homogenate.Histopathology shows molsid-omine treatment maintained normal architecture of sciatic nerve.The results of our study strengthens the alterative use of molsidomine in diabetic neuropathy.展开更多
BACKGROUND Although the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)induces more rapid liver regeneration than portal vein embolization,the mechanism remains unclear.AIM To assess...BACKGROUND Although the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)induces more rapid liver regeneration than portal vein embolization,the mechanism remains unclear.AIM To assess the influence of inflammatory cytokines and endothelial nitric oxide synthase(eNOS)activation on liver regeneration in ALPPS.METHODS The future liver remnant/body weight(FLR/BW)ratio,hepatocyte proliferation,inflammatory cytokine expression,and activation of the Akt-eNOS pathway were evaluated in rat ALPPS and portal vein ligation(PVL)models.Hepatocyte proliferation was assessed based on Ki-67 expression,which was confirmed using immunohistochemistry.The serum concentrations of inflammatory cytokines were measured using enzyme linked immune-solvent assays.The Akt-eNOS pathway was assessed using western blotting.To explore the role of inflammatory cytokines and NO,Kupffer cell inhibitor gadolinium chloride(GdCl3),NOS inhibitor N-nitro-arginine methyl ester(L-NAME),and NO enhancer molsidomine were administered intraperitoneally.RESULTS The ALPPS group showed significant FLR regeneration(FLR/BW:1.60%±0.08%,P<0.05)compared with that observed in the PVL group(1.33%±0.11%)48 h after surgery.In the ALPPS group,serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group.However,the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3(1.72%±0.19%,P<0.05;22.25%±1.30%,P<0.05)than in the PVL group(1.33%±0.11%and 12.78%±1.55%,respectively).Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group compared with those in the PVL group.There was no difference between the ALPPS group treated with L-NAME and the PVL group in the FLR/BW ratio and Ki-67 labeling index.In the PVL group treated with molsidomine,the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group.CONCLUSION Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration after ALPPS,whereas Akt-eNOS pathway activation may contribute to accelerated regeneration of the FLR.展开更多
文摘Diabetic neuropathy is a disorder which affects various regions of the nervous sys-tem and there is no specific treatment available for it.So,the present study eval-uated protective effect of molsidomine in diabetic neuropathy in rats.Diabetes was induced in male Wistar rats by administrating streptozotocin(52 mg/kg i.p).Diabetic rats were administered with molsidomine 5 mg/kg p.o,and 10mg/kg p.o.as treatment.After 8 weeks of treatment,Motor coordination,Mechanical allodynia,Mechanical hyperalgesia,Nerve conduction velocity,Glycosylated hemoglobin were assessed.Thereafter animals were sacrificed and sciatic nerve was isolated.It was used for reduced glutathione,lipid peroxidation and for histopathology.Treatment with molsidomine significantly improved motor coordination,paw withdrawal threshold,mechanical threshold and nerve conduction velocity.Furthermore,mol-sidomine treatment also reduced malondialdehyde levels and prevented depletion of reduced glutathione in sciatic nerve homogenate.Histopathology shows molsid-omine treatment maintained normal architecture of sciatic nerve.The results of our study strengthens the alterative use of molsidomine in diabetic neuropathy.
文摘BACKGROUND Although the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)induces more rapid liver regeneration than portal vein embolization,the mechanism remains unclear.AIM To assess the influence of inflammatory cytokines and endothelial nitric oxide synthase(eNOS)activation on liver regeneration in ALPPS.METHODS The future liver remnant/body weight(FLR/BW)ratio,hepatocyte proliferation,inflammatory cytokine expression,and activation of the Akt-eNOS pathway were evaluated in rat ALPPS and portal vein ligation(PVL)models.Hepatocyte proliferation was assessed based on Ki-67 expression,which was confirmed using immunohistochemistry.The serum concentrations of inflammatory cytokines were measured using enzyme linked immune-solvent assays.The Akt-eNOS pathway was assessed using western blotting.To explore the role of inflammatory cytokines and NO,Kupffer cell inhibitor gadolinium chloride(GdCl3),NOS inhibitor N-nitro-arginine methyl ester(L-NAME),and NO enhancer molsidomine were administered intraperitoneally.RESULTS The ALPPS group showed significant FLR regeneration(FLR/BW:1.60%±0.08%,P<0.05)compared with that observed in the PVL group(1.33%±0.11%)48 h after surgery.In the ALPPS group,serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group.However,the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3(1.72%±0.19%,P<0.05;22.25%±1.30%,P<0.05)than in the PVL group(1.33%±0.11%and 12.78%±1.55%,respectively).Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group compared with those in the PVL group.There was no difference between the ALPPS group treated with L-NAME and the PVL group in the FLR/BW ratio and Ki-67 labeling index.In the PVL group treated with molsidomine,the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group.CONCLUSION Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration after ALPPS,whereas Akt-eNOS pathway activation may contribute to accelerated regeneration of the FLR.
