<div style="text-align:justify;"> <strong>Background: </strong><span "="">To determine whether muscle contraction-induced leg blood flow (LBF) during exercise may be al...<div style="text-align:justify;"> <strong>Background: </strong><span "="">To determine whether muscle contraction-induced leg blood flow (LBF) during exercise may be altered in a patient with an ischemic limb due to peripheral arterial disease (PAD) compared with the non-PAD limb. <b>Case Presentation: </b>A 66-year-old male patient with intermittent claudication due to PAD in the right leg (ankle brachial pressure index, 0.69) showed complete obstruction in both common iliac arteries including internal/external segments with collaterals above the femoral artery and popliteal artery with collaterals, and in the healthy left non-PAD-leg (1.06). He attempted unilateral repeat isometric knee extensions at a target contraction rhythm with each leg at incremental contraction intensities (5%, 10%, and 30% of maximum voluntary contraction [MVC] for 3 min at each intensity). Blood velocity/flow (Doppler ultrasound) in the femoral artery, blood pressure, and leg vascular conductance (LVC) were measured. Isometric thigh MVC strength pre-exercise was similar between the PAD-leg (48.0 kg) and non-PAD-leg (48.7 kg). Pre-exercise LBF (ml/min) was also similar between the PAD-leg (316) and non-PAD-leg (327). Blood pressure increases were similar during exercise. Average exercising LBF in ml/min in the last 1 min at each intensity was higher in the PAD-leg than the non-PAD-leg: 1087 vs. 471 at 5%, 2097 vs. 712 at 10%, and 2656 vs. 1517 at 30% MVC with a close positive linear relationship between LBF and %MVC in the non-PAD-leg (r = 0.999, P</span> <span "="">< 0.01), in agreement with previous findings, but less significant in the PAD-leg (r = 0.879, P = NS), indicating intense vasodilation (increasing LVC) in the PAD-leg compared with the non-PAD-leg. <b>Conclusion: </b>Knee extensor exercising LBF in the femoral artery was dissimilar between the PAD-leg and non-PAD-leg at the same exercise intensity, even though pre-exercising LBF was the same. Further research on the time-course in hemodynamics during leg exercise in PAD might potentially provide insight for the cardiovascular adjustment in severity of arteriosclerosis, stenosis and/or collaterals reserve.</span> </div>展开更多
The arterial supply of the genicular meniscus was studied with macro-microanatomical and histological examinations,translucent preparations and scanning electronmicroscopy.It was found that the menisci were supplied b...The arterial supply of the genicular meniscus was studied with macro-microanatomical and histological examinations,translucent preparations and scanning electronmicroscopy.It was found that the menisci were supplied by the articular branches of thepopliteal artery except the lateral superior genicular branch and the descending genicularartery.Among them there were two genicular branches with independent stems from thepopliteal artery,named as the posterior medial and posterior lateral genicular artery,whichsupplied the posterior part of the corresponding meniscus.The genicular branchesanastomosed with each other to form a vascular circle around the menisci,and minutebranches from the circle formed an arterial network around the menisci and terminated incapillaries in 3 types of anastomotic forms.The surgical approach to the menisci and theprognosis of an injured meniscus were discussed on the basis of the arterial distributionsinside and outside of the menisci.展开更多
Inhibition of Notch1 signaling has been shown to promote astrocyte-derived neurogenesis after stroke.To investigate the regulatory role of Notch1 signaling in this process,in this study,we used a rat model of stroke b...Inhibition of Notch1 signaling has been shown to promote astrocyte-derived neurogenesis after stroke.To investigate the regulatory role of Notch1 signaling in this process,in this study,we used a rat model of stroke based on middle cerebral artery occlusion and assessed the behavior of reactive astrocytes post-stroke.We used theγ-secretase inhibitor N-[N-(3,5-diuorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester(DAPT)to block Notch1 signaling at 1,4,and 7 days after injury.Our results showed that only administration of DAPT at 4 days after stroke promoted astrocyte-derived neurogenesis,as manifested by recovery of white matter fiber bundle integrity on magnetic resonance imaging,which is consistent with recovery of neurologic function.These findings suggest that inhibition of Notch1 signaling at the subacute stage post-stroke mediates neural repair by promoting astrocyte-derived neurogenesis.展开更多
Knee dislocations frequently involve vascular injuries that demand early diagnosis and timely intervention. Time of ischemia is pivotal in determining the outcome for the limb, delays in treatment beyond 8 hours signi...Knee dislocations frequently involve vascular injuries that demand early diagnosis and timely intervention. Time of ischemia is pivotal in determining the outcome for the limb, delays in treatment beyond 8 hours significantly increase the risk of limb loss. Unfortunately, this critical window is often missed in resource-limited settings. Here we report a 25-year-old female sustained a left knee injury after falling into a trench. She was diagnosed with an open knee dislocation accompanied by a popliteal artery injury. However, revascularization was delayed for 18 hours due to limited resources, including the unavailability of a thrombectomy catheter. Postoperatively, the patient received anticoagulation therapy with serial limb assessments and after 3 weeks the laceration healed and the limb was still viable. Knee dislocations frequently result in vascular injury (popliteal artery most common), making prompt diagnosis and intervention essential for limb preservation. In settings with limited resources, like ours, delayed presentation and transfer to specialized centers contribute to prolonged ischemic times. Nonetheless, viable limbs should be revascularized in stable patients, even with prolonged ischemia. This case highlights the importance of limb revascularization despite delay. Efforts should be made to improve prompt diagnosis, timely referral, and availability of necessary equipment for vascular repair to optimize outcomes in similar cases.展开更多
目的评价腘动脉-膝关节后囊间隙(infiltration between the popliteal artery and the capsule of the posterior knee,iPACK)阻滞对比关节周围注射(periarticular injection,PAI)在全膝关节置换(total knee arthroplasty,TKA)术后镇痛...目的评价腘动脉-膝关节后囊间隙(infiltration between the popliteal artery and the capsule of the posterior knee,iPACK)阻滞对比关节周围注射(periarticular injection,PAI)在全膝关节置换(total knee arthroplasty,TKA)术后镇痛中的作用。方法检索PubMed、EMBASE、Web of Science、中国生物医学文献数据库(CBM)、中文科技期刊全文数据库(VIP)、中国期刊全文数据库(CNKI)及万方数据库中iPACK对比PAI对TKA术后镇痛的随机对照试验(RCT),时间均从建库至2021年12月。2位研究者按照纳入标准筛选文献、提取资料,2位评价员独立对纳入文献的质量进行评价,采用RevMan5.3进行meta分析。结果纳入6个RCT共440例患者。与PAI相比,iPACK组术后24 h吗啡累积使用量较少(MD=-4.21,95%CI:-7.18~-1.24,P=0.005),术后12 h运动状态和24、48 h静息状态、运动状态下疼痛视觉模拟评分(Visual Analogue Scale,VAS)降低,差异有统计学意义(P<0.05),术后12 h静息状态VAS差异无统计学意义(P>0.05);2组术后第1天、第2天行走距离相当,差异无统计学意义(P>0.05)。结论与PAI相比,iPACK阻滞能更有效地减轻TKA术后疼痛,减少阿片类药物用量,不影响术后活动,用于TKA术后镇痛安全有效。展开更多
AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(...AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.展开更多
Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia,but the mechanism underlying this relationship is unclea r.In this study,we found that miR-324-3p expression was d...Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia,but the mechanism underlying this relationship is unclea r.In this study,we found that miR-324-3p expression was decreased in patients with acute ischemic stroke and in in vitro and in vivo models of ischemic stro ke.miR-324-3p agomir potentiated ischemic brain damage in rats subjected to middle cerebral artery occlusion,as indicated by increased infarct volumes and cell apoptosis rates and greater neurological deficits.In a PC12 cell oxygen-glucose deprivation/reoxygenation model,a miR-324-3 p mimic decreased cell viability and expression of the anti-apoptotic protein BCL2 and increased expression of the pro-apoptotic protein BAX and rates of cell apoptosis,whereas treatment with a miR-324-3p inhibitor had the opposite effects.Silencing miR-324-3p increased adenosine A1 receptor(A1R)expression thro ugh regulation of GATA binding protein 2(GATA2).These findings suggest that silencing miR-324-3p reduces ischemic brain damage via the GATA2/A1R axis.展开更多
Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hyp...Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hypertension （PAH） and discuss the underlying mechanisms preliminarily. Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg^-1 monocrotaline （MCT）. One week later, the rats were administrated with 1, 3, 10 mg · kg^-1 DL0805-2 via intraperitoneal injection for 18 days. At the end of the experiment, the body weight and survival rate were recorded. Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected. Serum was collected for biochemical index analysis. The weight of vital organs was used to calculate the organ index. Histopathology examination was em-ployed to observe the subtle changes in hearts, vessels and lungs. Furthermore, the mechanisms were studied main- ly by the method of western blotting. Results DL0805-2 did not show significant influence on body weight of PAH rats. But the survival rate of PAH rats treated with 3 and 10 mg · kg^-1 DL0805-2 was increased up to 90. 9% com- pared with the model group （68.2%）. DL0805-2 improved the pulmonary artery blood flow especially the maximal -1 -1 velocity （PV max） from 397.2 cm · s^-1 to 506.5, 540. 1 and 574.0 cm · s^-1 respectively. The results of echocar- diography and electrocardiogram show that DL0805-2 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and 46.45 mmHg respectively after DL0805-2 intervention. Disease markers of PAH including NT-proBNP in serum and ET-1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL0805-2. DL0805-2 also relieved edema of lungs and decreased inflammatory cytokines production. Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension. Ac- cording to the preliminary study on the mechanisms of DL0805-2 in PAH, Rho/ROCK pathway was significantly in- hibited by DL0805 derivatives. In addition, DL0805 derivatives showed effect on BMPRII/p-Smad pathway and ap- optosis related pathway. Conclusion DL0805-2 has showed potent treatment effect on the PAH rats. And the un- derlying mechanisms studies also indicated that RhoA/ROCK and BMPRII pathways were involved. This work will provide basis experimental data for the further research and development of DL0805-2.展开更多
Study was carried out in rabbits to determine whether 3,4’,5-trihydroxystibene-3-β-nono-D-glucoside(PD)has wasodilative action using volumetric method.The result showed PD(1.71 mol/L)caused a right shift of the cumu...Study was carried out in rabbits to determine whether 3,4’,5-trihydroxystibene-3-β-nono-D-glucoside(PD)has wasodilative action using volumetric method.The result showed PD(1.71 mol/L)caused a right shift of the cumulative concentration-reponse curve of uorepinephfine(NE)and lowered the maximal response of rabbit’s pulmonary arteries.It implies that PD couldinhibit the vasoconstfictive effect of NE in a noncompetitive manner.PD dilated the pulmonaryarteries(4.09 and 5.12mmol/L)and the carotid(5.12mmol/L)of rabbits.This PD-induced relax-ation of puhnonary artenes was weakened by propranolol(87.8μmol/L).展开更多
文摘<div style="text-align:justify;"> <strong>Background: </strong><span "="">To determine whether muscle contraction-induced leg blood flow (LBF) during exercise may be altered in a patient with an ischemic limb due to peripheral arterial disease (PAD) compared with the non-PAD limb. <b>Case Presentation: </b>A 66-year-old male patient with intermittent claudication due to PAD in the right leg (ankle brachial pressure index, 0.69) showed complete obstruction in both common iliac arteries including internal/external segments with collaterals above the femoral artery and popliteal artery with collaterals, and in the healthy left non-PAD-leg (1.06). He attempted unilateral repeat isometric knee extensions at a target contraction rhythm with each leg at incremental contraction intensities (5%, 10%, and 30% of maximum voluntary contraction [MVC] for 3 min at each intensity). Blood velocity/flow (Doppler ultrasound) in the femoral artery, blood pressure, and leg vascular conductance (LVC) were measured. Isometric thigh MVC strength pre-exercise was similar between the PAD-leg (48.0 kg) and non-PAD-leg (48.7 kg). Pre-exercise LBF (ml/min) was also similar between the PAD-leg (316) and non-PAD-leg (327). Blood pressure increases were similar during exercise. Average exercising LBF in ml/min in the last 1 min at each intensity was higher in the PAD-leg than the non-PAD-leg: 1087 vs. 471 at 5%, 2097 vs. 712 at 10%, and 2656 vs. 1517 at 30% MVC with a close positive linear relationship between LBF and %MVC in the non-PAD-leg (r = 0.999, P</span> <span "="">< 0.01), in agreement with previous findings, but less significant in the PAD-leg (r = 0.879, P = NS), indicating intense vasodilation (increasing LVC) in the PAD-leg compared with the non-PAD-leg. <b>Conclusion: </b>Knee extensor exercising LBF in the femoral artery was dissimilar between the PAD-leg and non-PAD-leg at the same exercise intensity, even though pre-exercising LBF was the same. Further research on the time-course in hemodynamics during leg exercise in PAD might potentially provide insight for the cardiovascular adjustment in severity of arteriosclerosis, stenosis and/or collaterals reserve.</span> </div>
文摘The arterial supply of the genicular meniscus was studied with macro-microanatomical and histological examinations,translucent preparations and scanning electronmicroscopy.It was found that the menisci were supplied by the articular branches of thepopliteal artery except the lateral superior genicular branch and the descending genicularartery.Among them there were two genicular branches with independent stems from thepopliteal artery,named as the posterior medial and posterior lateral genicular artery,whichsupplied the posterior part of the corresponding meniscus.The genicular branchesanastomosed with each other to form a vascular circle around the menisci,and minutebranches from the circle formed an arterial network around the menisci and terminated incapillaries in 3 types of anastomotic forms.The surgical approach to the menisci and theprognosis of an injured meniscus were discussed on the basis of the arterial distributionsinside and outside of the menisci.
基金supported by the National Natural Science Foundation of China,Nos.81801660(to XZH)and 81771788(to YMY)。
文摘Inhibition of Notch1 signaling has been shown to promote astrocyte-derived neurogenesis after stroke.To investigate the regulatory role of Notch1 signaling in this process,in this study,we used a rat model of stroke based on middle cerebral artery occlusion and assessed the behavior of reactive astrocytes post-stroke.We used theγ-secretase inhibitor N-[N-(3,5-diuorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester(DAPT)to block Notch1 signaling at 1,4,and 7 days after injury.Our results showed that only administration of DAPT at 4 days after stroke promoted astrocyte-derived neurogenesis,as manifested by recovery of white matter fiber bundle integrity on magnetic resonance imaging,which is consistent with recovery of neurologic function.These findings suggest that inhibition of Notch1 signaling at the subacute stage post-stroke mediates neural repair by promoting astrocyte-derived neurogenesis.
文摘Knee dislocations frequently involve vascular injuries that demand early diagnosis and timely intervention. Time of ischemia is pivotal in determining the outcome for the limb, delays in treatment beyond 8 hours significantly increase the risk of limb loss. Unfortunately, this critical window is often missed in resource-limited settings. Here we report a 25-year-old female sustained a left knee injury after falling into a trench. She was diagnosed with an open knee dislocation accompanied by a popliteal artery injury. However, revascularization was delayed for 18 hours due to limited resources, including the unavailability of a thrombectomy catheter. Postoperatively, the patient received anticoagulation therapy with serial limb assessments and after 3 weeks the laceration healed and the limb was still viable. Knee dislocations frequently result in vascular injury (popliteal artery most common), making prompt diagnosis and intervention essential for limb preservation. In settings with limited resources, like ours, delayed presentation and transfer to specialized centers contribute to prolonged ischemic times. Nonetheless, viable limbs should be revascularized in stable patients, even with prolonged ischemia. This case highlights the importance of limb revascularization despite delay. Efforts should be made to improve prompt diagnosis, timely referral, and availability of necessary equipment for vascular repair to optimize outcomes in similar cases.
文摘目的评价腘动脉-膝关节后囊间隙(infiltration between the popliteal artery and the capsule of the posterior knee,iPACK)阻滞对比关节周围注射(periarticular injection,PAI)在全膝关节置换(total knee arthroplasty,TKA)术后镇痛中的作用。方法检索PubMed、EMBASE、Web of Science、中国生物医学文献数据库(CBM)、中文科技期刊全文数据库(VIP)、中国期刊全文数据库(CNKI)及万方数据库中iPACK对比PAI对TKA术后镇痛的随机对照试验(RCT),时间均从建库至2021年12月。2位研究者按照纳入标准筛选文献、提取资料,2位评价员独立对纳入文献的质量进行评价,采用RevMan5.3进行meta分析。结果纳入6个RCT共440例患者。与PAI相比,iPACK组术后24 h吗啡累积使用量较少(MD=-4.21,95%CI:-7.18~-1.24,P=0.005),术后12 h运动状态和24、48 h静息状态、运动状态下疼痛视觉模拟评分(Visual Analogue Scale,VAS)降低,差异有统计学意义(P<0.05),术后12 h静息状态VAS差异无统计学意义(P>0.05);2组术后第1天、第2天行走距离相当,差异无统计学意义(P>0.05)。结论与PAI相比,iPACK阻滞能更有效地减轻TKA术后疼痛,减少阿片类药物用量,不影响术后活动,用于TKA术后镇痛安全有效。
基金Supported by Peking Union Medical College Hospital Deposit Integration Commission Funds(No.ZC201904168).
文摘AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.
基金funded by the National Natural Science Foundation of China,No.81803937(to YCM and QXD)Science and Technology Innovation Activity Plan for College Students of Zhejiang Province(Xinmiao Talent Plan),No.2020R413079(to AQZ)Wenzhou Science and Technology Plan Project,No.Y20210122(to QXD)。
文摘Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia,but the mechanism underlying this relationship is unclea r.In this study,we found that miR-324-3p expression was decreased in patients with acute ischemic stroke and in in vitro and in vivo models of ischemic stro ke.miR-324-3p agomir potentiated ischemic brain damage in rats subjected to middle cerebral artery occlusion,as indicated by increased infarct volumes and cell apoptosis rates and greater neurological deficits.In a PC12 cell oxygen-glucose deprivation/reoxygenation model,a miR-324-3 p mimic decreased cell viability and expression of the anti-apoptotic protein BCL2 and increased expression of the pro-apoptotic protein BAX and rates of cell apoptosis,whereas treatment with a miR-324-3p inhibitor had the opposite effects.Silencing miR-324-3p increased adenosine A1 receptor(A1R)expression thro ugh regulation of GATA binding protein 2(GATA2).These findings suggest that silencing miR-324-3p reduces ischemic brain damage via the GATA2/A1R axis.
文摘Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hypertension （PAH） and discuss the underlying mechanisms preliminarily. Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg^-1 monocrotaline （MCT）. One week later, the rats were administrated with 1, 3, 10 mg · kg^-1 DL0805-2 via intraperitoneal injection for 18 days. At the end of the experiment, the body weight and survival rate were recorded. Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected. Serum was collected for biochemical index analysis. The weight of vital organs was used to calculate the organ index. Histopathology examination was em-ployed to observe the subtle changes in hearts, vessels and lungs. Furthermore, the mechanisms were studied main- ly by the method of western blotting. Results DL0805-2 did not show significant influence on body weight of PAH rats. But the survival rate of PAH rats treated with 3 and 10 mg · kg^-1 DL0805-2 was increased up to 90. 9% com- pared with the model group （68.2%）. DL0805-2 improved the pulmonary artery blood flow especially the maximal -1 -1 velocity （PV max） from 397.2 cm · s^-1 to 506.5, 540. 1 and 574.0 cm · s^-1 respectively. The results of echocar- diography and electrocardiogram show that DL0805-2 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and 46.45 mmHg respectively after DL0805-2 intervention. Disease markers of PAH including NT-proBNP in serum and ET-1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL0805-2. DL0805-2 also relieved edema of lungs and decreased inflammatory cytokines production. Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension. Ac- cording to the preliminary study on the mechanisms of DL0805-2 in PAH, Rho/ROCK pathway was significantly in- hibited by DL0805 derivatives. In addition, DL0805 derivatives showed effect on BMPRII/p-Smad pathway and ap- optosis related pathway. Conclusion DL0805-2 has showed potent treatment effect on the PAH rats. And the un- derlying mechanisms studies also indicated that RhoA/ROCK and BMPRII pathways were involved. This work will provide basis experimental data for the further research and development of DL0805-2.
基金This project was supprted by the Natonal Natural Science Foundation of China No 3880738
文摘Study was carried out in rabbits to determine whether 3,4’,5-trihydroxystibene-3-β-nono-D-glucoside(PD)has wasodilative action using volumetric method.The result showed PD(1.71 mol/L)caused a right shift of the cumulative concentration-reponse curve of uorepinephfine(NE)and lowered the maximal response of rabbit’s pulmonary arteries.It implies that PD couldinhibit the vasoconstfictive effect of NE in a noncompetitive manner.PD dilated the pulmonaryarteries(4.09 and 5.12mmol/L)and the carotid(5.12mmol/L)of rabbits.This PD-induced relax-ation of puhnonary artenes was weakened by propranolol(87.8μmol/L).
