1.Role of TLR4/NF-κB signal pathway in the hippocampus injury of status epileptic rats
Chinese Journal of Neurology 2008;41(10):689-694
Objective To observe the expression of TLR4 and NF-κB in hippocampus injury of status epileptic rats and to study the regulating effect of PDTC on TLR4/NF-KB signal pathway and hippocampus injury, and to explore the role of TLR4/NF-κB signal pathway in the hippocampus injury of SE rats. Methods A hundred and six male Sprague-Dawley (SD) rats were randomly divided into control group (A), convulsion group (B), PDTC group (C), and group B were randomly divided into 4 subset groups (B1-B4), which would be executed at 4, 24, 48 and 72 hours after convulsion. Continuous epilepticus was induced by injecting lithium chloride and pilocarpine, and group C were daily injected with 100 mg/kg PDTC 30 minutes after convulsion stopped for 3 days. Then the histopathology changes in hippocampus were viewed by HE staining, TLR4 and NF-κB/p65 protein were detected by immunohistochemistry (IHC), the expression of TLR4 mRNA were detected by RT-PCR. Results Neuronal injury was observed after a long time of convulsion, and the change was increased gradually 72 hours after seizure, which was milder in group Cthan in group B4. The expression of TLB4 protein in group B (B1-B4 were 0.1287±0. 0260, 0. 1296± 0. 0285, 0. 1330±0. 0329 and 0. 1604±0. 0457, respectively) was significantly higher than in group A (0.0964±0.0324, t =0.0641-0.3236, all P<0.05), and that in group C (0.1271±0.0330) was much lower than in B4 group (t = -0. 0334, P <0. 01). The IHC staining of NF-κB/p65 showed that hippocampal neurons had positive expression in cell nucleus in group B compared with the group A (P < 0. 05), and the expression of NF-κB/p65 protein in group C was much lower than that in group B4 (P < 0. 01). The mRNA expression of TLB4 in rat hippocampus of group B were significantly elevated than that in group A (0. 268±0. 072, P < 0. 05), and the tendency was increased gradually, reaching the peak at 72 hours after seizure (1. 242±0. 100), and that in group C (0. 984±0. 263) was much lower than that in B4 group (t=-0.2578, P<0.01). There was a coincidence between the expression of TLB4 and NF-κB/ p65. Conclusions The increased expression of TLR4 and NF-κB/p65 in SE rat hippocampus may play an promotion role on the development of the hippocampus injury; PDTC can down regulate the expression of TLR4, and lessen the pathologic changes of hippocampus.
2.Effects of resveratrol on the expression of Toll-like receptor 4, NF-кB and Caspase-3 in the hippocampus of the status convulsion rat
Qin ZHOU ; Qin ZHANG ; Guangqian LI
Acta Anatomica Sinica 2014;(3):321-327
Objective To study the expression of toll-like receptor 4 (TLR4), nuclear factor κB (NF-кB) and Caspase-3 and the change of neuron apoptosis of the hippocampus in the status convulsion rat , and to explore the effect of resveratrol on them.Methods A total of 106 male Sprague-Dawley(SD)rats were randomly divided into the control (A), convulsion (B) and resveratrol treatment (C) groups.Group B was further randomly divided into four subset groups (B1-B4) which were executed at 4h, 24h, 48h, 72h after convulsion discontinued .Continuous epilepticus was induced by injecting lithium chloride and pilocarpine , and group C was daily injected with 30mg/kg resveratrol 30minutes after convulsion stopped for 3 days.TLR4 and NF-κB/p65 proteins were detected by immunohistochemistry ( IHC ); the expressions of TLR4 and Caspase-3 mRNA were detected by RT-PCR.The neuron apoptosis was observed by TUNEL . Results The IHC staining of TLR4 protein in group B was significantly higher than in group A (P<0.05), and that in group C was much lower than in B 4 group ( P<0.01 ) .The expression of NF-кB/p65 showed that hippocampal neurons had positive expression in cell nuclei in group B compared with group A (P<0.05), and the expression of NF-кB/p65 protein in group C was much lower than that in group B 4 (P<0.01).The mRNA expressions of TLR4 and Caspase-3 in the rat hippocampus of group B were significantly elevated than that in group A ( P <0.05 ) , and the tendency was increased gradually , reaching the peak at 72 hours after seizure , and that in group C was much lower than that in B 4 group (P<0.01).The TUNEL positive cells in hippocampus CAl of B group were more than that of group A after the SC 24hours (P<0.01),reached the highest level at the 72nd hour, and that in group C the TUNEL positive cells were lower than that in B4 group (P<0.01).Conclusion The expression of TLR4, NF-кB and Caspase-3 increased after SC.Resveratrol can down regulate the expression of TLR4, NF-кB and Caspase-3 in the hippocampus with pilocarpine-induced seizures, reduced the number of neuronal apoptosis .These results suggest that resveratrol may have a protective effect against the hippocampus damage caused by status convulsion .
3.Effects of baicalin on glial fibrillary acidic protein and nuclear factor-κB expression in juvenile rat hippocampus after status convulsion
Zhuying ZHOU ; Xiuli CHEN ; Guangqian LI
Chinese Journal of Pathophysiology 2015;(8):1510-1515
[ABSTRACT]AIM:Tostudytheeffectsofbaicalin(BC)onglialfibrillaryacidicprotein(GFAP)andnuclear factor-κB ( NF-κB) expression and neuronal apoptosis in juvenile rat hippocampus after status convulsion ( SC) .METH-ODS:One hundred and ninety five juvenile male Sprague-Dawley rats were randomly divided into 3 groups:normal saline pretreatment group (NS group), SC group and SC with BC pretreatment group (BC group).Each of these 3 groups would be subdivided into 5 subgroups sacrificed at 4 h, 12 h, 24 h, 48 h and 72 h after SC.The rat SC model was prepared by lithium-pilocarpine chemical method .The protein expression of GFAP and NF-κB was detected by the method of immuno-histochemistry .The mRNA expression of GFAP was detected by RT-PCR.The neuronal apoptosis was observed by TdT-mediated dUTP nick end labeling ( TUNEL ) .RESULTS: Compared with NS group , the GFAP positive cells was in-creased in SC group (P<0.05).Compared with SC group, the expression of GFAP was significantly reduced in BC group (P<0.05).Compared with NS group, the NF-κB positive cells was increased in SC group (P<0.05).Compared with SC group, the expression of NF-κB was significantly reduced in BC group .RT-PCR showed that the expression trend of GFAP mRNA was similar to that of the protein .Compared with NS group , the TUNEL positive cells in the hippocampus CA1 area in SC group increased significantly 12 h after SC (P<0.01), and reached a peak at 48 h.After the intervention with BC, the TUNEL positive cells decreased significantly between 12~48 h after SC (P<0.05 or P<0.01), but the number of TUNEL positive cells remained significantly greater than that in NS group (P<0.05).CONCLUSION: The expression of GFAP and NF-κB in the hippocampus increased after SC in rats .Baicalin decreases the expression of GFAP and NF-κB in hippocampus of rats with pilocarpine-induced seizures , and reduces the number of neuronal apoptosis , sug-gesting that baicalin may protect against the brain damage caused by status convulsion .
4.Development of Therapy for Duchenne Muscular Dystrophy
Suzhen ZHANG ; Huiqi XIE ; Guangqian ZHOU ; Zhiming YANG
Chinese Journal of Reparative and Reconstructive Surgery 2007;21(2):194-203
Objective To review and summarize the latest development of the therapy for the Duchenne muscular dystrophy (DMD). Methods The recently-published articles related to the therapies for DMD were extensively reviewed and briefly summarized. Results The therapeutic approaches for DMD included the gene therapy, the cell therapy, and the pharmacological therapy.The gene therapy and the cell therapy were focused on the treatment for the cause of DMD by the delivery of the missing gene, the modification of the mutated gene, and the transfer of the normal cells including the stem cells, while the pharmacological therapy dealt with the downstream events caused by the dystrophin gene defect, slowed down the pathologic progress of DMD, and improved the DMD patient's life quality and life span, by medication and other factor treatments. Conclusion There is still no cure for DMD because of various difficulties in replacing or repairing the defected gene and of the multifaceted nature of the severe symptoms. Therefore, it is imperative for us to find out a more effective treatment that can solve these problems.
5.Expressions of glucose-regulated protein 78 and p38 mitogen-activated protein kinase signal pathway in the hippocampus of status convulsion rat and the effect of Nimodipine
Minhui XU ; Yanmin ZHAO ; Jingjing LOU ; Zhuying ZHOU ; Haiping WANG ; Guangqian LI
Chinese Journal of Applied Clinical Pediatrics 2015;30(5):384-388
Objective To explore the role of glucose-regulated protein 78 (GRP78),p38 mitogen-activated protein kinase(p38MAPK) signal pathway in seizure-reduced brain injures and the regulatory effect of Nimodipine on it.Methods Sprague-Dawley(SD) rats were randomly divided into status convulsion group (SC group),Nimodipine group(NM group),and a normal control group(NC group).The expressions of GRP78/Bip and p38MAPK mRNA and protein were detected by reverse transcription(RT)-PCR and immunohistochemistry.The expression of apoptosis cells was observed by TdT-mediated dUTP nick end labeling (TUNEL).Results (1) Immunohistochemistry:at 4 h after induction of status convulsion,the expression of GRP78 protein in the hippocampus CA1 domain began increasing slightly,and reached a maximum at 24 h,and then began decreasing slowly ; at 4 h after induction of status convulsion,the expression of p38MAPK protein in the hippocampus CA1 domain began increasing,and reached a maximum at 24 h,and decreased remarkably at 48 h.(2) RT-PCR:at 4 h after induction of status convulsion,the expression of GRP78 protein in the hippocampus CA1 domain began increasing slightly,and reached a maximum at 24 h,and then began decreasing slowly.The NM group was much higher than the SC group and the NC group(all P < 0.05) ; at 4 h after induction of status convulsion,the expression of p38MAPK protein in the hippocampus CA1 domain began increasing,and reached a maximum at 24 h,and decreased remarkably at 48 h;the NM group was much lower than the SC group,and higher than the NC group (all P < 0.05).(3) TUNEL:at 4 h after induction of status convulsion,the expression of the TUNEL positive cells in the hippocampus CA1 domain began increasing slightly,and reached a maximum at 48 h,and then began decreasing,and there was no difference between SC group and NC group;the NM group was much lower than the SC group(all P < 0.05).Conclusions The correlation of the increased expression of p38MAPK and neuronal apoptosis indicates that GRP78 signal pathway may be mediated to cell apoptosis through p38MAPK.Nimodipine can affect the expression of GRP78/Bip and p38MAPK,and relieve endoplasmic reticulum stress,and lessen the pathologic damage to the hippocampus.
6.The application of improved CHQS for mass epidemiology study on hearing impairment
Cheng LIU ; Guangqian XING ; Xia XU ; Zhibin CHEN ; Han ZHOU ; Dengyuan WANG ; Huiqin TIAN ; Xingkuan BU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2010;(1):19-20,24
Objective:To develop and evaluate the improved Chinese hearing questionnaire for school children(CHQS)for mass epidemiology study on hearing impairment in China.Method:Using the probability proportion to size(PPS) method, 8 412 residents were investigated in 40 clusters in Jiangsu province with the WHO ear diseases and hearing disorders survey protocol.87.9% of the residents aged 7 years and over answered the questionnaire and accepted the pure tone audiometry.Result:The prevalence of hearing impairment was 12.9% by the questionnaire. Compared with golden standard(pure tone audiometry), Sen=58.5%, Spe=96.7%, PV+=78.9%, PV-=91.7%, overall accuracy=90.0% . The sensitivity for women was higher than men.Conclusion:The questionnaire produced high efficiency and specificity values.It could be used in mass hearing screening, particularly in remote and rural area, although the sensitivity was as low as most questionnaires.
7.An epidemiologic study on tinnitus in aged population of Jiangsu province
Xia XU ; Xingkuan BU ; Guangqian XJNG ; Ling ZHOU ; Cheng LIU ; Dengyuan WANG ; Zhibin CHEN ; Han ZHOU ; Huiqin TIAN ; Xiaoiu LI ; Ling LU ; Xiaoman ZHAO ; Fangli LI ; Changqiang TAN
Chinese Journal of Geriatrics 2003;0(07):-
0. 05). Conclusions Tinnitus is a common problem in the older population. With the aging of population, the problem will become more and more severe. More research is urgently needed on prevention and treatment of tinnitus in elderly people.
8.The application of improved CHQS for mass epidemiology study on hearing impairment.
Cheng LIU ; Guangqian XING ; Xia XU ; Zhibin CHEN ; Han ZHOU ; Dengyuan WANG ; Huiqin TIAN ; Xingkuan BU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2010;24(1):19-24
OBJECTIVE:
To develop and evaluate the improved Chinese hearing questionnaire for school children (CHQS) for mass epidemiology study on hearing impairment in China.
METHOD:
Using the probability proportion to size (PPS) method, 8412 residents were investigated in 40 clusters in Jiangsu province with the WHO ear diseases and hearing disorders survey protocol. 87.9% of the residents aged 7 years and over answered the questionnaire and accepted the pure tone audiometry.
RESULT:
The prevalence of hearing impairment was 12.9% by the questionnaire. Compared with "golden standard" (pure tone audiometry), Sen = 58.5%, Spe = 96.7%, PV+ = 78.9%, PV- = 91.7%, overall accuracy = 90.0%. The sensitivity for women was higher than men.
CONCLUSION
The questionnaire produced high efficiency and specificity values. It could be used in mass hearing screening, particularly in remote and rural area, although the sensitivity was as low as most questionnaires.
China
;
epidemiology
;
Female
;
Hearing Disorders
;
epidemiology
;
prevention & control
;
Humans
;
Male
;
Sensitivity and Specificity
;
Surveys and Questionnaires
9.Auditory neuropathy in deaf school students.
Junguo WANG ; Xingkuan BU ; Aidong ZHOU ; Guangqian XING ; Qiulan SHI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2007;21(10):457-459
OBJECTIVE:
To investigate incidents and clinical features of auditory neuropathy in Nanjing deaf school students.
METHOD:
Three hundred and fifty-eight deaf students in the school accepted the first examination including otoscopic examination, tympanometry and transiently evoked otoacoustic emissions (TEOAE) screening. Detailed audiological and vestibular evaluations including pure-tone audiometry, immittance audiometry and acoustic reflex measures, transiently evoked otoacoustic emissions (TEOAE), distortion product otoacoustic emissions (DPOAE), auditory brain stem response (ABR), electronystagmography (ENG) and vestibular evoked myogenic potential (VEMP) were given to whom had positive TEOAE screening.
RESULT:
Three hundred and twenty-three students entered the program of screening for auditory neuropathy. One student had positive TEOAE in single ear while the other two had positive TEOAE in both ears. In the screening stage,there were strong evidences in these three students with auditory neuropathy in the detailed audiological procedures.
CONCLUSION
Auditory neuropathy, which can also be found in deaf schools, is not as rare as we thought before. Early identification and intervention may help those children to avoid entering the deaf school and to return to normal society.
Adolescent
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Adult
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Audiometry, Pure-Tone
;
Child
;
China
;
epidemiology
;
Cochlear Microphonic Potentials
;
Deafness
;
epidemiology
;
physiopathology
;
Evoked Potentials, Auditory, Brain Stem
;
Female
;
Hearing Loss, Central
;
epidemiology
;
physiopathology
;
Humans
;
Male
;
Otoacoustic Emissions, Spontaneous
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Students
;
Young Adult
10.Myocardin Reverses Hypoxia-Inducible Factor-1α Mediated Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in Hypoxia Induced by Cobalt Chloride
Xiongcai ZHOU ; Chao LUO ; Junhong FAN ; Guangqian GAO ; Tao WANG ; Haibo ZHANG ; Anyang WEI
The World Journal of Men's Health 2023;41(2):363-372
Purpose:
We aimed to investigate the mechanism of phenotypic transformation of corporal cavernosum smooth muscle cells (CCSMCs) under hypoxic conditions in vitro.
Materials and Methods:
In this study, a hypoxia model was established using cobalt chloride (CoCl2). CCSMCs were treated with different concentrations of CoCl2 for varying time periods, and cell viability was assessed. Hypoxia-inducible factor-1α (HIF-1α), myocardin (Myocd) and phenotypic markers were detected in the CCSMCs. We also transfected the CCSMCs with si-HIF-1α and Ad-Myocd and evaluated the effects on phenotypic modulation of CCSMCs and the relationship between HIF-1α and Myocd was evaluated.
Results:
CoCl2 inhibited the viability of CCSMCs in a dose- and time-dependent manner, and treatment with 300 µM CoCl2 for 48 hours were the optimal conditions for establishing the hypoxia model. The results showed increased expression levels of HIF-1α and osteopontin and decreased Myocd, alpha-smooth muscle actin, and calponin levels in CCSMCs under hypoxia. HIF-1α knockdown reversed hypoxia-induced phenotypic transformation with elevated Myocd expression. Overexpression of Myocd also reversed the effect of hypoxia on the phenotypic switch, but did not affect HIF-1α expression.
Conclusions
Our findings showed that HIF-1α was involved in the effect of hypoxia induced by CoCl2 on CCSMC phenotypic modulation, and Myocd overexpression could inhibit this process. Thus, Myocd might be a potential therapeutic target for erectile dysfunction under hypoxia or HIF-1α activation.