1.Protective effects of TAK-242 against coronary microembolization in rat associated with involvement of TLR4/NF-κB signaling pathway
Xiantao WANG ; Lang LI ; Yuanxi LU ; Yuhan SUN ; Wenkai HE ; Jiabao LIANG
Chinese Journal of Emergency Medicine 2017;26(7):745-750
Objective To investigate the role of TLR4/NF-κB signaling pathway under the action of TAK-242 in the cardiomyocyte apoptosis after coronary micro-embolism (CME) in rats.Methods Fortyfive rats were randomized (random number) into three groups:sham operation,CME and CME plus TAK242 groups (n =15 per group).CME was induced by injecting polyethylene microspheres (42 μm) into the left ventricle except the sham group.CME plus TAK-242 group was treated with TAK-242 (2 mg/kg) via the tail vein of mice 30 min before CME modeling.Cardiac function was evaluated 6 h after operation.Tissue biopsy was stained with HBFP to measure the size of infarction area.TUNEL assay was used to detect cardiomyocyte apoptosis.Western blot and qPCR were used to evaluate the protein levels and mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3,respectively.Statistical analysis was performed using one-way analysis of variance followed by LSD-t test.Results Compared with the sham group,left ventricular ejection fraction (LVEF) in the CME group was significantly decreased [(68.91 ± 4.12) % vs.(84.80 ± 2.51) %,P < 0.05],and the infarction area (P < 0.05),the apoptosis index [(3.36 ± 0.63) % vs.(0.19 ± 0.08) %,P <0.05],the mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3 in CME group were increased significantly (all P < 0.05).Compared with CME group,LVEF in the CME plus TAK-242 group was significantly improved [(75.58 ± 5.01) % vs.(68.91 ± 4.12) %,P<0.05],and the infarction area [(8.58 ± 2.12) % vs.(14.65 ± 4.23) %,P<0.05],the apoptosis index [(1.43 ± 0.51) % vs.(3.36 ± 0.63) %,P < 0.05],the mRNA expressions of TLR4,NF-κB p65 and cleaved caspase-3 in CME + TAK-242 group were decreased significantly (all P < 0.05).Conclusions TAK-242 effectively improved CME-induced cardiac dysfunction by regulating TLR4/NF-κB signaling pathway and then reducing the cardiomyocyte apoptosis.
2.Role of TLR4 in process of colonic inflammation recovery induced by LPS
Wanglin LI ; Mengao LIU ; Jie CAO ; Ping YANG ; Xiaobin ZHENG ; Boye DONG ; Jiabao LU
Chinese Journal of Pathophysiology 2017;33(2):336-343
AIM: To study the roles of Toll-like receptor 4 ( TLR4 ) and TLR4 activator lipopolysaccharide ( LPS) in colonic inflammation recovery .METHODS:Normal intestinal epithelial cells were cultured with LPS in vitro. The subgroups of the intestinal epithelial cells with differential expression of TLR 4 ( low, normal and high ) were construc-ted by the technique of lentivirus transfection .The cells with normal and high expression of TLR 4 were induced by LPS for 0 h, 2 h and 4 h.Inflammatory cytokines TNF-α, IL-6 and IL-8 in the culture supernatant were detected by ELISA .The mRNA levels of TNF-α, IL-6, IL-8, IL-10 and IL-1βwere detected by qPCR .The cell mobility was also monitored by wound healing assay .RESULTS:The protein expression of TLR 4 was significantly higher after LPS treatment than that in control groups of both cells with TLR4 normal and high expression (P<0.05).The inflammatory cytokines TNF-α, IL-6, IL-8 and IL-1βat mRNA and protein levels were also significantly increased after LPS treatment compared with control group (P<0.05).The protein levels of TNF-α, IL-6 and IL-8 between the 2 groups were also different with statistical sig-nificance ( P<0.05 ) .Higher mobility was observed in the cells with TLR 4 high expression compared to control cells . CONCLUSION:LPS induction might play a role in the activation of TLR 4-mediated inflammatory pathways by up-regula-ting the expression of inflammatory cytokines at both transcriptional and translational levels .
3.Bone marrow mesenchymal stem cell transplantation for treatment of emphysema:intravenous versus intratracheal approach
Xiaojian ZHAO ; Caiping LU ; Weiwei CHU ; Yaxiao ZHANG ; Bing ZHANG ; Qiang ZHEN ; Guoliang TAN ; Renfeng WANG ; Jiabao LIU ; Lin WU
Chinese Journal of Tissue Engineering Research 2015;(14):2211-2215
BACKGROUND:Bone marrow mesenchymal stem cel s transplantation can inhibit experimental emphysema inflammatory reaction and apoptosis, and has been experimental y confirmed to treat severe lung function impairment. OBJECTIVE:To explore the inhibitory effects of bone marrow mesenchymal stem cel s transplantation via different ways on inflammatory reaction and apoptosis due to experimental emphysema. METHODS:Female Wistar rats were randomly divided into control group, intravenous group and endotracheal group fol owing model establishment using fumigation plus intratracheal instil ation of porcine pancreatic elastase. In the latter two groups, bone marrow mesenchymal stem cel s from male rats were injected via the tail vein and the trachea, respectively. In the control group, rats were given PBS via he tail vein and trachea. At 14 days after transplantation, pathological changes of rat lung tissues were observed, cel apoptotic index in alveolar wal cel s and tumor necrosis factorαlevel in the bronchoalveolar lavage fluid were detected. RESULTS AND CONCLUSION:Compared with the control group, in the intravenous and endotracheal groups,the pathological changes of lung tissues were relieved, tumor necrosis factorαlevel and apoptosis index were reduced significantly (P<0.01);but there were no differences between the intravenous and endotracheal groups (P>0.05). These findings indicate that bone marrow mesenchymal stem cel s transplantation via the tail vein and trachea both can exert obvious therapeutic effects on emphysema. Moreover, cel transplantation via the tail vein is more convenient and easier than that via the trachea in the treatment of emphysema.
4.Clinical Observations on Qin’s Scalp Eight-needle Acupuncture for the Treatment of Cancer Pain
Yan ZHANG ; Haiyin ZHAO ; Ji WU ; Yafang WANG ; Wang LU ; Hanbing SHEN ; Ke FEI ; Shenghong ZHANG ; Jiabao ZHANG
Shanghai Journal of Acupuncture and Moxibustion 2016;35(10):1222-1225
Objective To compare the clinical efficacies of Qin’s scalp eight-needle acupuncture versus conventional scalp acupuncture in treating cancer pain. Method Sixty cancer pain patients with clinically or pathologically diagnosed malignant tumors were allocated, using a random number table, to a treatment (Qin’s scalp eight-needle acupuncture) group of 30 cases and a control (conventional scalp acupuncture) group of 30 cases. The treatment group received Qin’s scalp eight-needle acupuncture at selected points every other day and the control group, conventional scalp acupuncture every other day. One course of treatment consisted of 10 days. Result Cancer pain was relieved, analgesic dosage decreased, adverse reactions to analgesics reduced and quality of life raised significantly in the treatment group compared with the control group. Conclusion Qin’s scalp eight-needle acupuncture is effective in treating cancer pain.
5.Bone marrow mesenchymal stem cell transplantation suppresses emphysema-induced inflammation and apoptosis
Xiaojian ZHAO ; Caiping LU ; Weiwei CHU ; Qiang ZHEN ; Guoliang TAN ; Yaxiao ZHANG ; Renfeng WANG ; Bing ZHANG ; Jiabao LIU
Chinese Journal of Tissue Engineering Research 2014;(6):906-911
BACKGROUND:Bone marrow mesenchymal stem cells transplantation can change the surrounding microenvironment through paracrine mechanisms, and can be employed for treatment of serious damage to lung function through the promotion of angiogenesis, inhibition of apoptosis and maintaining functional stability of autonomic nervous system. OBJECTIVE:To observe the inflammatory reaction in experimental emphysema and inhibition of apoptosis through bone marrow mesenchymal stem cells transplantation.
METHODS:Twenty-four Wistar female rats were randomly divided into three groups:healthy control group, model group and experimental group. In the latter two groups, smoking and endotracheal instil ation of porcine pancreatic elastase were performed to establish emphysema models. After modeling, bone marrow mesenchymal stem cells were injected via tail vein in the experimental group. Pathological changes of the lung, the level of tumor necrosis factor-alpha and cellnumber in the bronchoalveolar lavage fluid as wel as apoptotic index in lveolar wal s were detected after celltransplantation.
RESULTS AND CONCLUSION:In the model and experimental groups, pathological changes of lung tissues were observed to different extent. The lung pathological changes were slighter in the experimental group than the model group (P<0.01). The level of tumor necrosis factor-alpha and apoptotic index in lung tissue were lower in the experimental group than the model group (P<0.01). These findings indicate that bone marrow mesenchymal stem cells can improve emphysema pathological y through inhibition of inflammatory response and apoptosis in experimental emphysema.