The γ-aminobutyric acid neurotransmitter in the spinal cord dorsal horn plays an important role in pain modulation through primary afferent-mediated presynaptic inhibition. The weakening of γ-aminobutyric acid-media...The γ-aminobutyric acid neurotransmitter in the spinal cord dorsal horn plays an important role in pain modulation through primary afferent-mediated presynaptic inhibition. The weakening of γ-aminobutyric acid-mediated presynaptic inhibition may be an important cause of neuropathic pain. γ-aminobutyric acid-mediated presynaptic inhibition is related to the current strength of γ-aminobutyric acid A receptor activation. In view of this, the whole-cell patch-clamp technique was used here to record the change in muscimol activated current of dorsal root ganglion neurons in a chronic constriction injury model. Results found that damage in rat dorsal root ganglion neurons following application of muscimol caused concentration-dependent activation of current, and compared with the sham group, its current strength and γ-aminobutyric acid A receptor protein expression decreased. Immunofluorescence revealed that γ-aminobutyric acid type A receptor α2 subunit protein expression decreased and was most obvious at 12 and 15 days after modeling. Our experimental findings confirmed that the y-aminobutyric acid type A receptor α2 subunit in the chronic constriction injury model rat dorsal root ganglion was downregulated, which may be one of the reasons for the reduction of injury in dorsal root ganglion neurons following muscimol-activated currents.展开更多
BACKGROUND： Studies have demonstrated that in vitro cultured cortical neurons from embryonic rats can produce spontaneous recurrent epileptiform discharges following transient Mg^2＋-free extracellular solution cultu...BACKGROUND： Studies have demonstrated that in vitro cultured cortical neurons from embryonic rats can produce spontaneous recurrent epileptiform discharges following transient Mg^2＋-free extracellular solution culture. OBJECTIVE： To explore gammaminobutyric acid A receptor （GABAAR）γ 2 subunit expression following Mg^2＋-free-induced seizures in cultured developing neurons. DESIGN, TIME AND SETTING： Cellular and molecular biology. The in vitro experiment was performed at the Department of Pediatrics, Second Xiangya Hospital of Central Southern University between January 2007 and February 2008. MATERIALS： Cortical neurons of Wistar rats on gestational days 16-17 were used. Normal extracellular solution （pH 7.3） consisted of NaCl 145 mmol/L, KCl 2.5 mmol/L, HEPES l0 mmol/L, MgC12 1 mmol/L, CaC12 2 mmol/L, glucose 10 mmol/L, and glycine 0.01 mmol/L. In addition, there was no MgCl2 in the Mg^2＋-free extracellular solution. METHODS： Cortical neurons cultured for 6 days were exposed to normal extracellular solution （control group） and Mg^2＋-free media （Mg^2＋-free group） respectively for 3 hours, followed by continuous culture in DMEM solution. MAIN OUTCOME MEASURES： On days 1, 7 and 12 after Mg^2＋-free treatment, real-time RT-PCR, immunochemistry, and flow cytometry were used to detect GABAAR 3/2 subunit expression. RESULTS： Compared with the control group, GABAAR γ-positive cells decreased significantly on days 1 and 7 after Mg^2＋-free treatment （P 〈 0.01）, but significantly increased on day 12 （P 〈 0.01 ）. GABAAR γ2 subunit mRNA expression decreased significantly at 7 days Mg^2＋-free treatment when measured by real-time RT-PCR compared with the control group （P 〈 0.05）. CONCLUSION： GABAAR γ2 subunit expression is modified following Mg-free-induced seizures in cultured developing neurons. This indicates the possibility that abnormal GABAA receptor expression might play an important role in development of neuronal injury.展开更多
Objective To study the effect of chronic noise exposure on expression of N-methyI-D-aspartic acid receptor 2B （NR2B） and tau phosphorylation in hippocampus of rats. Methods Twenty-four male SD rats were divided in c...Objective To study the effect of chronic noise exposure on expression of N-methyI-D-aspartic acid receptor 2B （NR2B） and tau phosphorylation in hippocampus of rats. Methods Twenty-four male SD rats were divided in control group and chronic noise exposure group. NR2B expression and tau phosphorylation in hippocampus of rats were detected after chronic noise exposure （100 dB SPL white noise, 4 h/dx30d） and their mechanisms underlying neuronal apoptosis in hippocampus of rats with TUNEL staining. Results The NR2B expression decreased significantly after chronic noise exposure which resulted in tau hyperphosphorylation and neural apoptosis in hippocampus of rats. Immunohistochemistry showed that the tau hyperphosphorylation was most prominent in dentate gyrus （DG） and CA1 region of rat hippocampus. Conclusion The abnormality of neurotransmitter system, especially Glu and NR2B containing NMDA receptor, and tau hyperphosphorylation in hippocampus of rats, may play a role in chronic noise-induced neural apoptosis and cognition impairment.展开更多
Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine.The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior,electroencephalography ...Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine.The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior,electroencephalography and 24-hour survival rate.Propofol（12.5-100 mg/kg） improved status epilepticus in a dose-dependent manner,and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection.Western blot results showed that,24 hours after induction of status epilepticus,the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus.Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels,but not the increase in N-methyl-D-aspartate receptor 2A subunit levels.The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine.This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures.展开更多
Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B （NR2B） overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA （siRNA） can inhibit NR2B e...Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B （NR2B） overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA （siRNA） can inhibit NR2B expression, siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury. However, an efficient and safe vector for NR2B siRNA has not been discovered. This study shows that a water soluble lipopolymer （WSLP） comprised of low molecular weight polyethyleneimine （PEI） and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP/siRNA complexes for 3 days inhibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respectively, compared with control rats （P 〈 0.01）. Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3, 7, 12, and 21 days, while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.展开更多
Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery.Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy.It a...Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery.Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy.It also reduces scar tissue formation and promotes axonal regeneration after spinal cord injury.The aim of the present study was to investigate the effect and mechanism of the microtubule-stabilizing reagent epothilone B in decreasing fibrotic scarring through its action on pericytes after spinal cord injury.A rat model of spinal cord injury was established via dorsal complete transection at the T10 vertebra.The rats received an intraperitoneal injection of epothilone B（0.75 mg/kg） at 1 and 15 days post-injury in the epothilone B group or normal saline in the vehicle group.Neuron-glial antigen 2,platelet-derived growth factor receptor β,and fibronectin protein expression were dramatically lower in the epothilone B group than in the vehicle group,but β-tubulin protein expression was greater.Glial fibrillary acidic protein at the injury site was not affected by epothilone B treatment.The Basso,Beattie,and Bresnahan locomotor scores were significantly higher in the epothilone B group than in the vehicle group.The results of this study demonstrated that epothilone B reduced the number of pericytes,inhibited extracellular matrix formation,and suppressed scar formation after spinal cord injury.展开更多
Bushen Tiansui decoction is composed of six traditional Chinese medicines：Herba Epimedii,Radix Polygoni multiflori,Plastrum testudinis,Fossilia Ossis Mastodi,Radix Polygalae,and Rhizoma Acorus tatarinowii.Because Bus...Bushen Tiansui decoction is composed of six traditional Chinese medicines：Herba Epimedii,Radix Polygoni multiflori,Plastrum testudinis,Fossilia Ossis Mastodi,Radix Polygalae,and Rhizoma Acorus tatarinowii.Because Bushen Tiansui decoction is effective against amyloid beta（Aβ） toxicity,we hypothesized that it would reduce hippocampal synaptic damage and improve cognitive function in Alzheimer＇s disease.To test this hypothesis,we used a previously established animal model of Alzheimer＇s disease,that is,microinjection of aggregated Aβ25–35 into the bilateral brain ventricles of Sprague-Dawley rats.We found that long-term（28 days） oral administration of Bushen Tiansui decoction（0.563,1.688,and 3.375 g/m L;4 m L/day） prevented synaptic loss in the hippocampus and increased the expression levels of synaptic proteins,including postsynaptic density protein 95,the N-methyl-D-aspartate receptor 2 B subunit,and Shank1.These results suggested that Bushen Tiansui decoction can protect synapses by maintaining the expression of these synaptic proteins.Bushen Tiansui decoction also ameliorated measures reflecting spatial learning and memory deficits that were observed in the Morris water maze（i.e.,increased the number of platform crossings and the amount of time spent in the target quadrant and decreased escape latency） following intraventricular injections of aggregated Aβ25–35 compared with those measures in untreated Aβ_（25–35）-injected rats.Overall,these results provided evidence that further studies on the prevention and treatment of dementia with this traditional Chinese medicine are warranted.展开更多
Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows...Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 receptor(P<0.01).Conclusions:Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction,and the mechanism can be attributed,in part,to the increased expression of the GABAB2 receptor.展开更多
Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports tha...Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports that antipsychotic aripiprazole(Ari)against the proliferation of CRC cells both in vitro and in vivo,but with less damage in normal colon cells.Mechanistically,the results showed that5-hydroxytryptamine 2B receptor(HTR2B)and its coupling protein G protein subunit alpha q(Gaq)were highly distributed in CRC cells.Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling.Blockade of HTR2B signaling suppressed the growth of CRC cells,but HTR2B was not found to have independent anticancer activity.Interestingly,the binding of Gaq to HTR2B was decreased after Ari treatment.Knockdown of Gaq not only restricted CRC cell growth,but also directly affected the antiCRC efficacy of Ari.Moreover,an interaction between Ari and Gaq was found in that the mutation at amino acid 190 of Gaq reduced the efficacy of Ari.Thus,these results confirm that Gaq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation.Collectively,this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.展开更多
基金supported by the Youth Science and Technology Innovation Special Foundation of Xinjiang Production and Construction Corps, China, No. 2010JC33
文摘The γ-aminobutyric acid neurotransmitter in the spinal cord dorsal horn plays an important role in pain modulation through primary afferent-mediated presynaptic inhibition. The weakening of γ-aminobutyric acid-mediated presynaptic inhibition may be an important cause of neuropathic pain. γ-aminobutyric acid-mediated presynaptic inhibition is related to the current strength of γ-aminobutyric acid A receptor activation. In view of this, the whole-cell patch-clamp technique was used here to record the change in muscimol activated current of dorsal root ganglion neurons in a chronic constriction injury model. Results found that damage in rat dorsal root ganglion neurons following application of muscimol caused concentration-dependent activation of current, and compared with the sham group, its current strength and γ-aminobutyric acid A receptor protein expression decreased. Immunofluorescence revealed that γ-aminobutyric acid type A receptor α2 subunit protein expression decreased and was most obvious at 12 and 15 days after modeling. Our experimental findings confirmed that the y-aminobutyric acid type A receptor α2 subunit in the chronic constriction injury model rat dorsal root ganglion was downregulated, which may be one of the reasons for the reduction of injury in dorsal root ganglion neurons following muscimol-activated currents.
基金the National Natural Science Foundation of China,No.30400483
文摘BACKGROUND： Studies have demonstrated that in vitro cultured cortical neurons from embryonic rats can produce spontaneous recurrent epileptiform discharges following transient Mg^2＋-free extracellular solution culture. OBJECTIVE： To explore gammaminobutyric acid A receptor （GABAAR）γ 2 subunit expression following Mg^2＋-free-induced seizures in cultured developing neurons. DESIGN, TIME AND SETTING： Cellular and molecular biology. The in vitro experiment was performed at the Department of Pediatrics, Second Xiangya Hospital of Central Southern University between January 2007 and February 2008. MATERIALS： Cortical neurons of Wistar rats on gestational days 16-17 were used. Normal extracellular solution （pH 7.3） consisted of NaCl 145 mmol/L, KCl 2.5 mmol/L, HEPES l0 mmol/L, MgC12 1 mmol/L, CaC12 2 mmol/L, glucose 10 mmol/L, and glycine 0.01 mmol/L. In addition, there was no MgCl2 in the Mg^2＋-free extracellular solution. METHODS： Cortical neurons cultured for 6 days were exposed to normal extracellular solution （control group） and Mg^2＋-free media （Mg^2＋-free group） respectively for 3 hours, followed by continuous culture in DMEM solution. MAIN OUTCOME MEASURES： On days 1, 7 and 12 after Mg^2＋-free treatment, real-time RT-PCR, immunochemistry, and flow cytometry were used to detect GABAAR 3/2 subunit expression. RESULTS： Compared with the control group, GABAAR γ-positive cells decreased significantly on days 1 and 7 after Mg^2＋-free treatment （P 〈 0.01）, but significantly increased on day 12 （P 〈 0.01 ）. GABAAR γ2 subunit mRNA expression decreased significantly at 7 days Mg^2＋-free treatment when measured by real-time RT-PCR compared with the control group （P 〈 0.05）. CONCLUSION： GABAAR γ2 subunit expression is modified following Mg-free-induced seizures in cultured developing neurons. This indicates the possibility that abnormal GABAA receptor expression might play an important role in development of neuronal injury.
基金supported by a grant from the National Natural Science Foundation of China (No. 81001237)
文摘Objective To study the effect of chronic noise exposure on expression of N-methyI-D-aspartic acid receptor 2B （NR2B） and tau phosphorylation in hippocampus of rats. Methods Twenty-four male SD rats were divided in control group and chronic noise exposure group. NR2B expression and tau phosphorylation in hippocampus of rats were detected after chronic noise exposure （100 dB SPL white noise, 4 h/dx30d） and their mechanisms underlying neuronal apoptosis in hippocampus of rats with TUNEL staining. Results The NR2B expression decreased significantly after chronic noise exposure which resulted in tau hyperphosphorylation and neural apoptosis in hippocampus of rats. Immunohistochemistry showed that the tau hyperphosphorylation was most prominent in dentate gyrus （DG） and CA1 region of rat hippocampus. Conclusion The abnormality of neurotransmitter system, especially Glu and NR2B containing NMDA receptor, and tau hyperphosphorylation in hippocampus of rats, may play a role in chronic noise-induced neural apoptosis and cognition impairment.
基金supported by National Natural Science Foundation of China,No. 30500482
文摘Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine.The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior,electroencephalography and 24-hour survival rate.Propofol（12.5-100 mg/kg） improved status epilepticus in a dose-dependent manner,and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection.Western blot results showed that,24 hours after induction of status epilepticus,the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus.Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels,but not the increase in N-methyl-D-aspartate receptor 2A subunit levels.The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine.This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures.
基金the Natural Science Foundation of Guangdong Province,No.07000059the Science and Technology Development Program of Guangzhou,No.2010Y1-C301the Science and Technology Development Program of Guangdong Province,No.2010B031600123
文摘Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B （NR2B） overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA （siRNA） can inhibit NR2B expression, siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury. However, an efficient and safe vector for NR2B siRNA has not been discovered. This study shows that a water soluble lipopolymer （WSLP） comprised of low molecular weight polyethyleneimine （PEI） and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP/siRNA complexes for 3 days inhibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respectively, compared with control rats （P 〈 0.01）. Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3, 7, 12, and 21 days, while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.
基金supported by a grant from the Science and Technology Developing Program of Shandong Provincial Government of China,No.2010GSF10254a grant from the Medical and Health Science and Technology Plan Project of Shandong Province of China,No.2015WS0504
文摘Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery.Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy.It also reduces scar tissue formation and promotes axonal regeneration after spinal cord injury.The aim of the present study was to investigate the effect and mechanism of the microtubule-stabilizing reagent epothilone B in decreasing fibrotic scarring through its action on pericytes after spinal cord injury.A rat model of spinal cord injury was established via dorsal complete transection at the T10 vertebra.The rats received an intraperitoneal injection of epothilone B（0.75 mg/kg） at 1 and 15 days post-injury in the epothilone B group or normal saline in the vehicle group.Neuron-glial antigen 2,platelet-derived growth factor receptor β,and fibronectin protein expression were dramatically lower in the epothilone B group than in the vehicle group,but β-tubulin protein expression was greater.Glial fibrillary acidic protein at the injury site was not affected by epothilone B treatment.The Basso,Beattie,and Bresnahan locomotor scores were significantly higher in the epothilone B group than in the vehicle group.The results of this study demonstrated that epothilone B reduced the number of pericytes,inhibited extracellular matrix formation,and suppressed scar formation after spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.81373705the Natural Science Foundation of Hunan Province in China,No.13JJ3030
文摘Bushen Tiansui decoction is composed of six traditional Chinese medicines：Herba Epimedii,Radix Polygoni multiflori,Plastrum testudinis,Fossilia Ossis Mastodi,Radix Polygalae,and Rhizoma Acorus tatarinowii.Because Bushen Tiansui decoction is effective against amyloid beta（Aβ） toxicity,we hypothesized that it would reduce hippocampal synaptic damage and improve cognitive function in Alzheimer＇s disease.To test this hypothesis,we used a previously established animal model of Alzheimer＇s disease,that is,microinjection of aggregated Aβ25–35 into the bilateral brain ventricles of Sprague-Dawley rats.We found that long-term（28 days） oral administration of Bushen Tiansui decoction（0.563,1.688,and 3.375 g/m L;4 m L/day） prevented synaptic loss in the hippocampus and increased the expression levels of synaptic proteins,including postsynaptic density protein 95,the N-methyl-D-aspartate receptor 2 B subunit,and Shank1.These results suggested that Bushen Tiansui decoction can protect synapses by maintaining the expression of these synaptic proteins.Bushen Tiansui decoction also ameliorated measures reflecting spatial learning and memory deficits that were observed in the Morris water maze（i.e.,increased the number of platform crossings and the amount of time spent in the target quadrant and decreased escape latency） following intraventricular injections of aggregated Aβ25–35 compared with those measures in untreated Aβ_（25–35）-injected rats.Overall,these results provided evidence that further studies on the prevention and treatment of dementia with this traditional Chinese medicine are warranted.
基金supported by the Shanghai Science&Technology Commission(18140902502)the National Key Research and Development Program of China(2016YFC1303100)+2 种基金the National Natural Science Foundation of China(81472423)the Shanghai Clinical and Medical Center of Key Program(2017ZZ01016)the Shanghai Science and Technology Innovation Project of Traditional Chinese Medicine(ZYKC201701020).
文摘Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 receptor(P<0.01).Conclusions:Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction,and the mechanism can be attributed,in part,to the increased expression of the GABAB2 receptor.
基金supported by Chongqing basic research and frontier exploration project(cstc2022ycjh-bgzxm0119,China)。
文摘Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports that antipsychotic aripiprazole(Ari)against the proliferation of CRC cells both in vitro and in vivo,but with less damage in normal colon cells.Mechanistically,the results showed that5-hydroxytryptamine 2B receptor(HTR2B)and its coupling protein G protein subunit alpha q(Gaq)were highly distributed in CRC cells.Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling.Blockade of HTR2B signaling suppressed the growth of CRC cells,but HTR2B was not found to have independent anticancer activity.Interestingly,the binding of Gaq to HTR2B was decreased after Ari treatment.Knockdown of Gaq not only restricted CRC cell growth,but also directly affected the antiCRC efficacy of Ari.Moreover,an interaction between Ari and Gaq was found in that the mutation at amino acid 190 of Gaq reduced the efficacy of Ari.Thus,these results confirm that Gaq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation.Collectively,this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.
