Background There are two major pathological hallmarks of AIzheimer＇s disease. One is the progressive accumulation of beta-amyloid （Aβ） in the form of senile plaques; the other is hyperphosphorylated tau, causing n...Background There are two major pathological hallmarks of AIzheimer＇s disease. One is the progressive accumulation of beta-amyloid （Aβ） in the form of senile plaques; the other is hyperphosphorylated tau, causing neuronal apoptosis. Some inhalation anesthetics, such as isoflurane and desfiurane, have been suggested to induce Aβaccumulation and cause AD-like neuropathogenesis. Whether intravenous anesthetics have similar effects is still unclear. We therefore set out to determine the relationship between propofol and AD-like pathogenesis. Methods PC12 cells were cultured in serum-free medium for 12 hours prior to drug treatment. Various concentrations from 5 IJmol/L to 80 μmol/L of aggregated Aβ2s.ss were added to determine a proper concentration for further study. After exposure to 10μmol/L Aβ25-35 alone or with 20 μmol/L propofol for 6 hours, PC12 cell viability was determined by MTT assay. Western blotting and immunocytochemical staining were performed to observe the protein expression of the Bcl-2 family, tau phosphorylation at different sites, and tau protein kinases and phosphatases. Results Aβ25-35 induced a decrease in PC12 cell viability in a dose-dependent manner. Exposure to 10 pmol/L Aβ25-35 for 6 hours resulted in the mild cell survival, accompanied by a decline in Bcl-2, and an increase in phosphorylation of GSK-313 and tau at different sites. Compared with the Aβ25-35 group, cells treated with propofol alone showed no significant difference, while cells co-incubated with propofol and Aβ25-35 showed a significantly higher survival rate （P 〈0.01 or P 〈0.05）. Tau phosphorylation at Ser396, Ser404 and Thr231 and the level of GSK-3β in PC12 cells increased after exposure to 10 IJmol/L β25-35. Co-incubation with propofol attenuated cellular apoptosis by inhibiting tau phosphorylation. Conclusions These data indicate that propofol may protect PC12 cells fromβ25-35-induced apoptosis and tau hyperphosphorylation through the GSK-313 pathway, therefore it may be a safer anesthesia for AD and elderly patients.展开更多
Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether...Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca^2＋/calmodulin-dependent protein kinase Ⅱ （CaMKⅡ） contributes to the analgesic effect of gabapentin on a chronic constriction injury （CCI） model. Methods Gabapentin （2%, 100 mg/kg） or saline （0.5 ml/100 g） was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0-4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKⅡ were quantified by reverse-transcriptional polymerase chain reaction and Western blotting. Results The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKⅡ and phosphorylated CaMKⅡ in CCI rats. Conclusion The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKⅡ in the spinal cord.展开更多
基金The present study was supported by the grants from the National Nature Science Foundation of China （No. 30872425） and Janssen Research Council China Foundation and Libang Anesthesiology R＆D Platform of Chinese Society of Anesthesiolgoy, Chinese Medical Association.
文摘Background There are two major pathological hallmarks of AIzheimer＇s disease. One is the progressive accumulation of beta-amyloid （Aβ） in the form of senile plaques; the other is hyperphosphorylated tau, causing neuronal apoptosis. Some inhalation anesthetics, such as isoflurane and desfiurane, have been suggested to induce Aβaccumulation and cause AD-like neuropathogenesis. Whether intravenous anesthetics have similar effects is still unclear. We therefore set out to determine the relationship between propofol and AD-like pathogenesis. Methods PC12 cells were cultured in serum-free medium for 12 hours prior to drug treatment. Various concentrations from 5 IJmol/L to 80 μmol/L of aggregated Aβ2s.ss were added to determine a proper concentration for further study. After exposure to 10μmol/L Aβ25-35 alone or with 20 μmol/L propofol for 6 hours, PC12 cell viability was determined by MTT assay. Western blotting and immunocytochemical staining were performed to observe the protein expression of the Bcl-2 family, tau phosphorylation at different sites, and tau protein kinases and phosphatases. Results Aβ25-35 induced a decrease in PC12 cell viability in a dose-dependent manner. Exposure to 10 pmol/L Aβ25-35 for 6 hours resulted in the mild cell survival, accompanied by a decline in Bcl-2, and an increase in phosphorylation of GSK-313 and tau at different sites. Compared with the Aβ25-35 group, cells treated with propofol alone showed no significant difference, while cells co-incubated with propofol and Aβ25-35 showed a significantly higher survival rate （P 〈0.01 or P 〈0.05）. Tau phosphorylation at Ser396, Ser404 and Thr231 and the level of GSK-3β in PC12 cells increased after exposure to 10 IJmol/L β25-35. Co-incubation with propofol attenuated cellular apoptosis by inhibiting tau phosphorylation. Conclusions These data indicate that propofol may protect PC12 cells fromβ25-35-induced apoptosis and tau hyperphosphorylation through the GSK-313 pathway, therefore it may be a safer anesthesia for AD and elderly patients.
基金This research is supported by a grant from the National Natural Science Foundation of China （No. 30672029）.
文摘Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca^2＋/calmodulin-dependent protein kinase Ⅱ （CaMKⅡ） contributes to the analgesic effect of gabapentin on a chronic constriction injury （CCI） model. Methods Gabapentin （2%, 100 mg/kg） or saline （0.5 ml/100 g） was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0-4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKⅡ were quantified by reverse-transcriptional polymerase chain reaction and Western blotting. Results The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKⅡ and phosphorylated CaMKⅡ in CCI rats. Conclusion The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKⅡ in the spinal cord.
