Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabe...Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin（30 and 100 mg/kg per day,intragastrically） for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase（n NOS,i NOS）,superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1（marker for increased microgliosis） in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity（Schwann cell marker） was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.展开更多
BACKGROUND： Researches on diabetic nervous system lesion are mainly focus on peripheral nerve and vegetative nerve, so there are few investigations on diabetic pseudotabes. OBJECTIVE： To investigate the electrophysi...BACKGROUND： Researches on diabetic nervous system lesion are mainly focus on peripheral nerve and vegetative nerve, so there are few investigations on diabetic pseudotabes. OBJECTIVE： To investigate the electrophysiological examinations on the diagnosis of diabetic pseudotabes. DESIGN： Case study. SETTING： Department of Electrophysiology and Department of Neurology, Zhongshan Hospital Affiliated to Xiamen University. PARTICIPANTS： A total of 4 patients with type 2 diabetes mellitus, including 3 males and 1 female aged from 50 to 72 years, were selected from Department of Neurology, Zhongshan Hospital Affiliated to Xiamen University from March 2002 to February 2005. All accepted subjects met the modified diagnostic criteria of diabetes mellitus, which was set by American Diabetes Mellitus Association （ADA） in 1997. Otherwise, the subjects had typical symptoms and physical signs of spinal posterior funiculus damage. However, patients with spinal cord lesion which was caused by other factors were excluded. All accepted subjects provided the confirmed consent. METHODS： Nicolet NT electromyography （EMG）/evoked potential meter （made in the USA） was used to detect spinal cord conduction velocity （SCCV）, somatosensory evoked potential （SEP） of lower limbs, motor nerve conduction velocity （MNCV） and sensory nerve conduction velocity （SNCV） of extremities. Determining criteria： Measurements were performed based on the laboratory standards. SCCV, which was less than lower limit of normal value （T2–12： 40–55 m/s, T12–L4： 20–41 m/s, T2–L4： 36–45 m/s）, was regarded as abnormal. SEP value of lower limbs： P40, P60 and PF, which were more than standard deviation of normal value （x — ＋2.5）, were regarded as the abnormality. Normal value of P40, P60 and PF latencies （x —±s） in this study： P40, P60 and PF in males were （37.6±1.9） ms, （59.8±3.9） ms and （7.6±0.9） ms, respectively; meanwhile, those in females were （35.5±1.7） ms, （55.2±2.7） ms and （6.3±0.7） ms, respectively. MNCV and SNCV, which were less than 50 m/s in upper limbs and 40 m/s in lower limbs, were regarded as the abnormality. MAIN OUTCOME MEASURES： Electrophysiological examinations. RESULTS： All 4 patients with type 2 diabetes mellitus were involved in the final analysis. ① SCCV： Among 4 patients, SCCV of three patients was decreased in T2–12, T12–L4 and T2–L4, and that of the other one was decreased in T2–12 and T2–L4; however, SCCV in T12–L4 was normal. There was significant difference as compared with normal value （P 〈 0.01）. ② SEP of lower limbs： SEP values of lower limbs were abnormal in all 4 patients. Among them, P40, P60 and PF latencies of two patients were delayed; P40 of one patient was delayed and PF was not drained out; P40 and P60 of the last one were delayed and PF was normal. ③ MNCV and SNCV： The MNCV and SNCV were normal in one patient and abnormal in three patients. The results demonstrated that MNCV and SNCV of extremities decreased; especially, sensory nerve action potential （SNAP） of both lower extremities of one patient were not drained out. CONCLUSION： Detections of SCCV, SEP of lower limbs, MNCV and SNCV of extremities are helpful to investigate whether peripheral nerve and deep sensory passage are damaged or not and determine whether deep sensory damage is caused by peripheral nerve and spinal posterior funiculus.展开更多
基金supported by the Research Fund of Ege University(Project No.2010-TIP-076)
文摘Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin（30 and 100 mg/kg per day,intragastrically） for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase（n NOS,i NOS）,superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1（marker for increased microgliosis） in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity（Schwann cell marker） was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.
文摘BACKGROUND： Researches on diabetic nervous system lesion are mainly focus on peripheral nerve and vegetative nerve, so there are few investigations on diabetic pseudotabes. OBJECTIVE： To investigate the electrophysiological examinations on the diagnosis of diabetic pseudotabes. DESIGN： Case study. SETTING： Department of Electrophysiology and Department of Neurology, Zhongshan Hospital Affiliated to Xiamen University. PARTICIPANTS： A total of 4 patients with type 2 diabetes mellitus, including 3 males and 1 female aged from 50 to 72 years, were selected from Department of Neurology, Zhongshan Hospital Affiliated to Xiamen University from March 2002 to February 2005. All accepted subjects met the modified diagnostic criteria of diabetes mellitus, which was set by American Diabetes Mellitus Association （ADA） in 1997. Otherwise, the subjects had typical symptoms and physical signs of spinal posterior funiculus damage. However, patients with spinal cord lesion which was caused by other factors were excluded. All accepted subjects provided the confirmed consent. METHODS： Nicolet NT electromyography （EMG）/evoked potential meter （made in the USA） was used to detect spinal cord conduction velocity （SCCV）, somatosensory evoked potential （SEP） of lower limbs, motor nerve conduction velocity （MNCV） and sensory nerve conduction velocity （SNCV） of extremities. Determining criteria： Measurements were performed based on the laboratory standards. SCCV, which was less than lower limit of normal value （T2–12： 40–55 m/s, T12–L4： 20–41 m/s, T2–L4： 36–45 m/s）, was regarded as abnormal. SEP value of lower limbs： P40, P60 and PF, which were more than standard deviation of normal value （x — ＋2.5）, were regarded as the abnormality. Normal value of P40, P60 and PF latencies （x —±s） in this study： P40, P60 and PF in males were （37.6±1.9） ms, （59.8±3.9） ms and （7.6±0.9） ms, respectively; meanwhile, those in females were （35.5±1.7） ms, （55.2±2.7） ms and （6.3±0.7） ms, respectively. MNCV and SNCV, which were less than 50 m/s in upper limbs and 40 m/s in lower limbs, were regarded as the abnormality. MAIN OUTCOME MEASURES： Electrophysiological examinations. RESULTS： All 4 patients with type 2 diabetes mellitus were involved in the final analysis. ① SCCV： Among 4 patients, SCCV of three patients was decreased in T2–12, T12–L4 and T2–L4, and that of the other one was decreased in T2–12 and T2–L4; however, SCCV in T12–L4 was normal. There was significant difference as compared with normal value （P 〈 0.01）. ② SEP of lower limbs： SEP values of lower limbs were abnormal in all 4 patients. Among them, P40, P60 and PF latencies of two patients were delayed; P40 of one patient was delayed and PF was not drained out; P40 and P60 of the last one were delayed and PF was normal. ③ MNCV and SNCV： The MNCV and SNCV were normal in one patient and abnormal in three patients. The results demonstrated that MNCV and SNCV of extremities decreased; especially, sensory nerve action potential （SNAP） of both lower extremities of one patient were not drained out. CONCLUSION： Detections of SCCV, SEP of lower limbs, MNCV and SNCV of extremities are helpful to investigate whether peripheral nerve and deep sensory passage are damaged or not and determine whether deep sensory damage is caused by peripheral nerve and spinal posterior funiculus.
