1.Study on the simulated high load and weightlessness exposure on intervertebral discs imaging and matrix metalloporteinase and its inhibitor expression in New Zealand white rabbits
Xuanyu CHEN ; Chao ZHENG ; Mingkui DU ; Zhenhua ZHANG ; Xiang JI ; Hui ZHAO ; Kaifeng JIN ; Weitao ZHONG ; Liming ZHANG ; Ji WU
Chinese Journal of Aerospace Medicine 2022;33(1):8-17
Objective:To discuss the influence of high load and weightlessness environment on intervertebral disc by observing and analyzing the imaging changes of the spines in New Zealand white rabbits and the content changes of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) in the intervertebral disc under high load and weightlessness environment, and to provide theoretical basis for prevention and delay of lumbar intervertebral disc degeneration under high load and weightlessness environment.Methods:A total of 120 New Zealand white rabbits with balanced age and body weight were randomly and averagely divided into control groups (further grouped by 30 d, 60 d and 90 d) and high load/weightlessness groups (further grouped by 30 d, 60 d and 90 d) with residual single-blind method. High load was simulated by animal centrifuge and weightlessness was simulated by tail suspension. The imaging changes and the positive expression rates of MMP1, MMP3 and TIMP1 in intervertebral disc were detected, and the statistical differences between the high load/weightlessness group and the control group in different time periods were compared, as well as among the different exposure time in load/weightlessness groups.Results:From the imaging observation, the T2-weighted images of lumbar 6 sacral 1 intervertebral disc in experimental animals decreased to some extent. The positive rates of MMP1 and MMP3 in each high load/weightlessness group were higher than those in the control group for the same exposure time, and the differences were statistically significant ( t=22.97-145.51,all P<0.001). The positive rates of MMP1 and MMP3 increased with the extension of exposure time, and there were statistically differences among the groups with different exposure time in high load/weightlessness group ( F=2531.10, 1758.80, both P<0.001). The positive rate of TIMP1 in each high load/weightlessness group was higher than that in the control group for the same exposure time, and the difference was statistically significant ( t=29.34-65.05, all P<0.001). There was statistically difference on TIMP1 positive rate among different load/weightlessness exposure time groups ( F=462.20, P<0.001). Conclusions:High load/weightlessness can cause the MMP1, MMP3 and TIMP1 content changes in animal lumbar disc. The changes of TIMP1 are obvious in the early stage and the sensitivity is decreased in the late stage. High load/weightlessness may lead to changes in the contents of MMP and TIMP in intervertebral discs, which may accelerate intervertebral disc degeneration.
2.Study on the simulated high load and weightlessness exposure on intervertebral discs imaging and matrix metalloporteinase and its inhibitor expression in New Zealand white rabbits
Xuanyu CHEN ; Chao ZHENG ; Mingkui DU ; Zhenhua ZHANG ; Xiang JI ; Hui ZHAO ; Kaifeng JIN ; Weitao ZHONG ; Liming ZHANG ; Ji WU
Chinese Journal of Aerospace Medicine 2022;33(1):8-17
Objective:To discuss the influence of high load and weightlessness environment on intervertebral disc by observing and analyzing the imaging changes of the spines in New Zealand white rabbits and the content changes of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) in the intervertebral disc under high load and weightlessness environment, and to provide theoretical basis for prevention and delay of lumbar intervertebral disc degeneration under high load and weightlessness environment.Methods:A total of 120 New Zealand white rabbits with balanced age and body weight were randomly and averagely divided into control groups (further grouped by 30 d, 60 d and 90 d) and high load/weightlessness groups (further grouped by 30 d, 60 d and 90 d) with residual single-blind method. High load was simulated by animal centrifuge and weightlessness was simulated by tail suspension. The imaging changes and the positive expression rates of MMP1, MMP3 and TIMP1 in intervertebral disc were detected, and the statistical differences between the high load/weightlessness group and the control group in different time periods were compared, as well as among the different exposure time in load/weightlessness groups.Results:From the imaging observation, the T2-weighted images of lumbar 6 sacral 1 intervertebral disc in experimental animals decreased to some extent. The positive rates of MMP1 and MMP3 in each high load/weightlessness group were higher than those in the control group for the same exposure time, and the differences were statistically significant ( t=22.97-145.51,all P<0.001). The positive rates of MMP1 and MMP3 increased with the extension of exposure time, and there were statistically differences among the groups with different exposure time in high load/weightlessness group ( F=2531.10, 1758.80, both P<0.001). The positive rate of TIMP1 in each high load/weightlessness group was higher than that in the control group for the same exposure time, and the difference was statistically significant ( t=29.34-65.05, all P<0.001). There was statistically difference on TIMP1 positive rate among different load/weightlessness exposure time groups ( F=462.20, P<0.001). Conclusions:High load/weightlessness can cause the MMP1, MMP3 and TIMP1 content changes in animal lumbar disc. The changes of TIMP1 are obvious in the early stage and the sensitivity is decreased in the late stage. High load/weightlessness may lead to changes in the contents of MMP and TIMP in intervertebral discs, which may accelerate intervertebral disc degeneration.
3.AngⅡin paraventricular nucleus contribute to chronic intermittent hypoxia induced-hypertension in rats
Xiaohai YU ; Yan LI ; Yang DING ; Zhiqiang TANG ; Jinli WANG ; Yifei FAN ; Wenhui CHENG ; Mingkui ZHONG
Chinese Pharmacological Bulletin 2015;(5):716-720
Aim To determine whether AngⅡin para-ventricular nucleus (PVN)was involved in the chronic intermittent hypoxia (CIH ) induced-hypertension in rats.Methods Male Sprague-Dawley rats were ran-domly divided into Sham and CIH groups,the Sham rats were exposed to continuous normoxia,while the CIH rats were submitted to CIH (8 h per day for 15 days).The conscious noninvasive method with tail cuff was performed in rats to record the systolic blood pres-sure during establishing the model of CIH induced hy-pertension.Mean arterial pressure (MAP)and heart rate (HR)were recorded in vivo on a PowerLab data acquisition system after CIH.Rats were fixed on the stereotaxic instrument to conduct microinjection in the PVN.We used Western blot to measure Ang Ⅱ level and AngⅡtype 1 receptor (AT1 R)protein expression in PVN.Results The level of PVN Ang Ⅱin CIH rats was significantly higher than that in Sham rats,a-long with increased AT1 R protein expression.Microin-jection of Ang Ⅱ(0.03,0.3,3 nmol)in bilateral PVN dose-dependently increased MAP in both CIH and Sham rats,and this response was significantly augmen-ted in CIH rats.Losartan (50 nmol),AT1 R antago-nist,had no effect on MAP in Sham rats,but caused significant MAP decreases in CIH rats,and prevented Ang Ⅱ-induced increases in MAP in both CIH and Sham rats.Conclusion The results suggest that the increased AngⅡrelease and enhanced AT1 R activation in the PVN contribute to CIH induced-hypertension in rats.
4.Effect of levothyroxine and vitamin E treatment on oxidative stress and myocardial apoptosis in rats with hypothyroidism
Tianrong PAN ; Chuanyuan CAI ; Yanqing ZHANG ; Mingkui ZHONG ; Minggong YANG ; Youmin WANG
Chinese Journal of Endocrinology and Metabolism 2012;28(7):584-588
Objective To investigate the oxidative stress status and cardiac myocyte apoptosis in rats with propylthiouracil-induced hypothyroidism and to examine the effect of levothyroxine ( LT4 ),vitamin E ( VitE ),and both supplementation on this experimental model.Methods Male Sprague Dawley rats were divided into normal control group( NC),propylthiouracil group( PTU ),LT4 treatment group( PTU + LT4 ),VitE treatment group ( PTU +VitE),LT4 and VitE combination therapy group (PTU + LT4 + VitE).Serum T3,T4,TSH levels,serum and myocardial superoxide dismutase ( SOD ) activity and malondialdehyde ( MDA ) content were determined.Cardiac myocyte apoptotic index was made with TUNEL.Results ( 1 ) Compared with NC group,T3 and T4 levels were significantly lower and TSH level was significantly higher in PTU group and PTU+VitE groups( P<0.05 ).Compared with PTU group,T3 and T4 levels were significantly higher and TSH level was significantly lower in PTU + LT4 group and PTU + LT4 + VitE group( P<0.05 ).There were no statistical differences in T3,T4,and TSH levels between PTU group and PTU + VitE group( P>0.05 ).( 2 ) Compared to NC group,serum and myocardial MDA levels in PTU group increased significantly( P<0.05 ),serum SOD activity decreased significantly ( P<0.05 ),while myocardial SOD activity showed no significant difference( P>0.05 ).( 3 ) Compared with NC group,myocardial apoptosis index was significantly higher in PTU and PTU + VitE groups( P<0.05 ).Compared with PTU group,myocardial apoptosis index was significantly lower in PTU + LT4 group and PTU + LT4 + VitE group( P<0.05 ).Conclusion LT4,VitE,and their combined treatment of hypothyroidism in rats reduce the myocardial cells apoptosis,which may be related to the improvement of thyroid function and amelioration of oxidative stress.
5.The role of serotonin in ventrolateral preoptic area on sleep-wakefulness cycle of rat
Gongliang ZHANG ; Yanlong HE ; Liecheng WANG ; Lezhang ZHAO ; Jing ZHANG ; Mingkui ZHONG ; Jingxing ZHANG
Chinese Pharmacological Bulletin 2003;0(08):-
AIM To study the role of serot on in (5-HT) in ventrolateral preoptic nucleus(VLPO) on sleep and wakefulness cycl e of rat by microinjection of 5-hydroxytryptaphan (5-HTP , precursor of 5-HT ) , non-special 5-HT receptor antagonist methysergide (MS) and 5-HT retake i nhibitor fluoxetine. METHODS Stereotaxic, microinjection and po lysomnography (PSG) were used in the experiment. RESULTS There was no significant effect by microinjection of 5-HTP(0 5 ?g,0 1 ?l) into VLPO,but microinjection of 5-HTP(1 ?g,0 1 ?l)and fluoxetine lead wake i ncreased and sleep decreased; while microinjection of non-selective serotonin receptor antagonist MS lead to the opposited effect. The chang of sleep-wakefu lness cycle caused by 5-HTP or MS were significantly assiociated with time. CONCLUSION 5-HT involved in the regulation of sleep-wake cycle a nd promoted wake in the VLPO and its role of promotion may involve the gene exp ression of post-synaptic neurons.
7.Impact of the CD4~+CD25~(nt/hi)CD127~(lo) regulatory T cells on the immune status and disease progression in HIV-1 infected individuals
Mingkui ZHOU ; Yile XUE ; Juli GONG ; Leiming ZHOU ; Xiaohong ZHENG ; Jing GAI ; Fangwei SHEN ; Wei ZHANG ; Zhen NING ; Qing YUE ; Wei LU ; Qichao PAN ; Laiyi KANG ; Ping ZHONG ; Wensi ZHU ; Ying WANG
Chinese Journal of Immunology 1999;0(12):-
Objective:To investigate the impact of the CD4+CD25nt/hiCD127lo regulatory T cell subset frequency on the immune status and disease progression of Chinese HIV-1 infected individuals.Methods:83 untreated HIV-infected individuals and 312 healthy control individuals of four distinct age groups were enrolled in the research. The CD4+ T cell absolute counts, phenotypes and frequency determination of CD4+CD25nt/hiCD127lo Regulatory T cell subsets was performed on freshly obtained whole blood samples by 3-color immune staining flow cytometry. The HIV-1 specific cellular immune function was test at single cell level by ELISpot. The corresponding plasma viral load was determined by NASBA.Results:The frequency of peripheral CD4+CD25nt/hiCD127lo regulatory T cells of HIV infected individuals in distinct disease progression status was dissimilar in China , and significantly increased in contrast to the healthy controls(P
8.Role of serotonergic projection from dorsal raphe nuclei to basolateral amygadaloid in regulation of sleep
Lezhang ZHAO ; Jun GAO ; Jingxing ZHANG ; Gongliang ZHANG ; Mingkui ZHONG ; Jin ZHANG ;
Chinese Pharmacological Bulletin 1987;0(01):-
AIM To investigate the role of serotonergic projection from dorsal raphe nuclei (DRN) to basolateral amygadaloid (BLA) in the regulation of sleep and waking state. METHODS stereotaxic microinjection and polysomnography were employed. RESULTS Microinjection of L Glu into the DRN caused an enhancement of wake (W) and a decrease of slow wave sleep (SWS) and paradoxical sleep (PS). However, microinjection of L Glu into the DRN plus bilateral microinjection of methysergide (MS) into the BLA reversed the effects of L Glu. Microinjection of PCPA into the DRN caused an enhancement of SWS and a decrease of W. Microinjection of PCPA into the DRN plus bilateral microinjection of 5 HTP into the BLA reversed the effects of PCPA. CONCLUSION These results suggest that the role of the DRN in the regulation of sleep and waking state is partly mediated by serotonergic projection from the DRN to the BLA.

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