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Objective To investigate the effect of BQ-123 on the ability of learning and memory and nerve cell autophagy in hippocam-pus in rats with subarachnoid hemorrhage (SAH). Methods 72 male Sprague-Dawley rats were randomly divided into sham group, SAH model group (SAH group) and BQ-123 group with 24 rats in each group. SAH model was established by injecting the autologous blood into cisterna magna twice. The sham group was not injected blood. BQ-123 group received intracerebroventricular injection with BQ-123 18μg 30 minutes before modeling. 6, 24, 72 and 144 hours after modeling, the passive avoidance latency (PAL) and active avoidance reaction rate (AARR) were tested with Shutter Box Test, the nerve cell morphological changes of hippocampus were observed with HE staining, and the expressions of Beclin-1 and LC3-II were detected with immunohistochemical staining. Results Compared with the sham group, the PAL pro-longed, the AARR decreased (P<0.05), the nerve cells in the hippocampus reduced (P<0.05), and the expressions of Beclin-1 and LC3-II in-creased (P<0.05) in SAH group. Compared with SAH group, PAL shortened (P<0.05), AARR increased (P<0.05), the nerve cells in the hip-pocampus increased (P<0.05), and the expressions of Beclin-1 and LC3-II increased (P<0.05) in BQ-123 group. Conclusion BQ-123 can promote the recovery of learning and memory ability, which may relate to the activation of nerve cell autophagy in the hippocampus.
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Objective To observe BQ123 on lung tissue injury following ischemia-reperfusion of hind limbs in rats.Methods A total of 30 male SD rats were randomly divided into control,I-R,and BQ123 groups,with 10 rats in each group. After 4- hour of ischemia and 4-hour of reperfusion to the hind limbs, ET-1 was measured by radioimmunoassay, levels of myeloperoxidase (MPO) and malondialehyde (MDA) were examined by biochemical method,and the content of P-selectin was examined by ELISA. Immunohistochemical method was used to detect the expressions of Fas,Bcl-2 and Caspase-3 in lung tissues. Pulmonary apoptosis was examined by means of TdT-mediated dUTP nick end labeling ( TUNEL) . Results Compared with the control group,the levels of ET-1,MPO,MDA and P-selectin in lung tissues were all increased significantly in I-R group ( P<0. 01). The expressions of Fas,Bcl-2 and Caspase-3 were 0. 294±0. 003,0. 108±0. 005,and 0. 174±0. 003,significantly up-regulated in the I-R group. The apoptosis rate [(18. 83±2. 86)%] was significantly increased in the I-R group (P<0. 01). Compared with I-R group,the tissue contents of ET-1,MPO,MDA and P-selectin were significantly lowered in BQ123 group (P<0. 01). The expression levels of Fas (0. 115±0. 007) and Caspase-3 (0. 159±0. 006) were decreased,but the expression of Bcl-2 was increased (0. 128±0. 005). The apoptosis rate in BQ123 group was significantly lower [(10. 67±2. 16)%,P<0. 01].Conclusion BQ123 may have protective effects on lung tissue after limb ischemia-reperfusion in rats by means of improving neutrophil aggregation and reducing the expression of proteins related to cell apoptosis.
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Aim To investigate the protection of ramipril,BQ-123 and their combination against myocardial ischemia/reperfusion(I/R)injury in vivo in anesthetized rats,and to explore the mechanism of action of drugs on myocardial oxidation-antioxidation system.Methods Healthy male Wistar rats were divided into 5 groups randomly,sham operated(Sham)group,I/R group,ramipril(RAM)group,BQ-123(BQ)group and ramipril and BQ-123(R&B)group.All groups but not sham were subjected to I/R procedure.Twenty four hours before ligation,ramipril(1 mg·kg~(-1))was intragastrically administered to rats in RAM and R&B groups.The equal volume of normal saline was given to rats in other groups.BQ-123(10 μg·kg~(-1)· min-1)was infused intravenously from 10 min before ligation to the end of 30 min ischemia to rats in BQ and R&B groups.The equal volume of normal saline was given to other groups.HR,MAP and the change of ST-segment were observed;ventricular arrhythmias were monitored during ischemia;the infarct size was examined by TTC staining;the activity of myocardial T-SOD,Mn-SOD,CAT and the content of MDA were detected by spectrophotometer.Results Compared with I/R group,the elevation of ST-segment was decreased,onset of VPC and VT was delayed,duration of VPC and VT was shortened,incidence of VPC,VT and VF was decreased,IS and IS/AAR were improved,activity of T-SOD,Mn-SOD and CAT was increased,the content of MDA was decreased in RAM,BQ and R&B groups.Compared with RAM and BQ alone group,onset of VPC and VT,duration of VPC and VT,size,activity of T-SOD and Mn-SOD and content of MDA were changed dramatically in R&B group.Conclusions Ramipril,BQ-123 and the combined use of these two agents protected myocardium from I/R injury in vivo.The protective effects of the combination on delaying onset of VA,shortening duration of VA,decreasing infarct size and content of MDA,and increasing activity of SOD are better than those of using ramipril or BQ-123 alone.
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BACKGROUND: Proliferation of vascular smooth muscle cells(VSMC) is a critical event in the development of atherosclerosis. Endothelin-1(ET-1), a vasoconstrictor peptide produced by endothelial cells and VSMC, might play a role in vascular remodeling. To investigate the proposed 'mitogenic' potential of ET-1, we examined the effects of ET-1 on the proliferation if cultured porcine aortic VSMC and on the potential synergism with platelet-derived growth factor(PDGF). MATERIALS AND METHODS: VSMC were obtained from porcine aorta and cultured in Dulbecco's modified Eagle medium supplmented with 10% fetal bovine serum(FBS). VSMC grown subconfluently in 12-well plate were stimulated by ET-1, PDGF, and ET-1 & PDGF and DNA synthesis was determined as the uptake of 3H-thymidine into cell cultures. We also examined the effects of BQ123, a selective ETA receptor antagonist, and NG-methyl-L-arginine(NMLA), a nitric oxide synthase (NOS) inhibitor. RESULTS: ET-1 elicited a 2.5-fold increase of cultured VSMC DNA synthesis, comparing with basal medium, and PDGF elicited a 4.8-fold increase, whereas ET-1 and PDGF elicited a 8.8-fold increase, showing synergistic effect. Proliferative activity of ET-1 on VSMC was blocked(39%) by BQ123, however, the synergistic effect of ET-1 and PDGF was not blocked by BQ123. The synergistic effect of ET-1 and PDGF was increased when co-stimulated with NMLA. CONCLUSION: ET-1 is a co-mitogen for VSMC from porcine aorta, whose proliferative activity requires serum or other growth factors such as PDGF for its maximal activity. The proliferative activity of ET-1 is considered to be transduced partly by selective activation of the ETA receptor, however, the synergistic effect of of ET-1 and PDGF is to be stimulated by non-ETA receptor.