Objective:To explore the possible mechanism of Huoxue Yiqi recipe promoting angiogenesis by targeting VEGF with miR-484.Methods:The model of miR-484 overexpressed in HUVEC was prepared and intervened with Huoxue Yiqi ...Objective:To explore the possible mechanism of Huoxue Yiqi recipe promoting angiogenesis by targeting VEGF with miR-484.Methods:The model of miR-484 overexpressed in HUVEC was prepared and intervened with Huoxue Yiqi Recipe Freeze-dried powder.The effects of Huoxue Yiqi Recipe on proliferation,migration and tubular forming ability of HUVEC were separatly detected by CCK-8 method,cell scratch test and Matrigel three-dimensional forming test in vitro.The effect of Huoxue Yiqi Recipe on VEGFA mRNA expression was detected by real-time fluorescence quantitative PCR.Results:Compared with the control group,the proliferation and migration area of cells in miR-484 overexpression model group decreased,the length,number of branches and nodes involved in tube formation decreased,the tube formation ability decreased significantly,and the expression level of VEGFA mRNA decreased,with statistical significance.Compared with the model group,the cell proliferation ability,migration area,length,number of branches and nodes involved in tube formation,tube formation ability and expression level of VEGFA mRNA in the Huoxue Yiqi Prescription group were up-regulated,and the difference was statistically significant(P<0.05).Conclusion:MiR-484 inhibits the expression of VEGFA and the proliferation,migration and formation of HUVEC,and Huoxue Yiqi recipe has a certain negative regulation effect on this process,which may be a new target of Huoxue Yiqi recipe to promote angiogenesis.展开更多
Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. Th...Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation （D 15, D 18 and D21）. The rats were randomly assigned into 3 groups： normal group, model group [fetal growth restriction （FGR） model], and Bushen Tqi Huoxue （BYHR） recipe treatment group （BYHR group, the pregnant rats with FGR were treated with BYHR recipe）. Morphological analysis indicated that during initial villous formation, fetal nucle- ated erythrocytes （FNEs） appeared in maternal blood sinus （MBS）. Subsequently, FNEs were sur- rounded by endothelial cells to form fetal capillary （FC） and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining （EIS） in normal and BYHR groups. Whereas, villous formation was suppressed, normal in- crease in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flkl mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while de- creased on D21 in model group as compared with normal group and BYHR group. Immunohistochemi- cally, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D 15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.展开更多
Objective: To objectively evaluate the efficacy of Huoxue Tongluo Recipe(活血通络方) in the treatment of chemotherapy-induced peripheral neuropathy(CIPN).Methods: A multicenter, randomized, double-blind, block, and pa...Objective: To objectively evaluate the efficacy of Huoxue Tongluo Recipe(活血通络方) in the treatment of chemotherapy-induced peripheral neuropathy(CIPN).Methods: A multicenter, randomized, double-blind, block, and parallel-controlled study was conducted in which 184 subjects who met the inclusion criteria were randomized into a trial group(92 cases), a control group(46 cases), a placebo group(46 cases) at a 2:1:1 ratio, respectively.Huoxue Tongluo Recipe(活血通络方) granules, Huangqi Guizhi Wuwu Decoction(黄芪桂枝五物汤) instant granules, placebo instant granules were given for hand and foot soaking, with water temperature 38 ℃-45 ℃, soaking for 20 minutes and the intervention time was 14 days.Results:(1) The total effective test drug was 41.30%, the control group was 32.61%, and the placebo group was 32.61%.There was no significant difference in the efficiency of the 3 groups by CMH chi-square test(P>0.05);(2) In the statistics of previous chemotherapy regimens including oxaliplatin or paclitaxel as stratification factors, the overall efficiency of the trial group was significantly different from the other 2 groups.Conclusion: Huoxue Tongluo Recipe(活血通络方) external washing can improve the peripheral nerve injury caused by chemotherapy to some extent, especially in patients with previous chemotherapy regimen including oxaliplatin and paclitaxel.展开更多
Background:Hypertension,a prevalent disease,is a significant risk factor for coronary heart disease.Huoxue Qianyang Qutan Recipe (HQQR),a traditional Chinese herbal remedy,has been used for treating hypertension over ...Background:Hypertension,a prevalent disease,is a significant risk factor for coronary heart disease.Huoxue Qianyang Qutan Recipe (HQQR),a traditional Chinese herbal remedy,has been used for treating hypertension over several years.Objective:This study assesses HQQR’s efficacy for controlling blood pressure among patients with hypertension related to blood stasis,yang hyperactivity and phlegm.Design,setting,participants and interventions:A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,from July 2020 to June 2022.Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography.Participants aged18–80 years,exhibiting traditional Chinese medicine syndromes of blood stasis,yang hyperactivity or phlegm,along with grades 1 or 2 hypertension,were randomly categorized into two groups.The intervention group was given HQQR granules alongside conventional hypertension treatment,while the control group was given placebo granules in addition to conventional treatment for 12 weeks.Main outcome measures:The primary outcome was clinic blood pressure,whereas secondary outcomes included metabolic indices (e.g.,homeostasis model assessment of insulin resistance[HOMA-IR],total cholesterol[TC],low-density lipoprotein cholesterol and triglyceride),target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio[UACR]) and inflammation indices(interleukin-6[IL-6]and high-sensitivity C-reactive protein[hs-CRP]).Results:HQQR’s primary components were identified as salvianolic acid B,emodin and ferulic acid.Of the 216 participants (108 in each group),compared to the control,the intervention group exhibited significant improvements (P<0.001) in clinic systolic blood pressure ([136.24±7.63]vs[130.06±8.50]mmHg),clinic diastolic blood pressure ([84.34±8.72]vs[80.46±6.05]mmHg),home systolic blood pressure([131.64±8.74]vs[122.36±8.45]mmHg) and home diastolic blood pressure ([78.47±9.53]vs[71.79±6.82]mm Hg).HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure:[133.75±10.49]vs[132.46±8.84]mmHg and 24-hour diastolic blood pressure:[84.12±8.01]vs[82.11±7.45]mmHg) and an improvement in HOMA-IR ([4.09±1.72]vs[3.98±1.44]),TC ([4.66±1.47]vs[3.75±1.81]mmol/L) and UACR (75.94[5.12,401.12]vs 45.61[4.26,234.26]).Moreover,HQQR demonstrated a decrease in hs-CRP (1.46[0.10,10.53]vs 0.57[0.12,3.99]mg/L) and IL-6 (6.69[2.00,29.74]vs 5.27[2.00,9.73]pg/mL),with no reported side effects (P<0.001).Conclusion:This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure,glycolipid metabolism,and inflammation in patients with hypertension.展开更多
OBJECTIVE:To elucidate the mechanism by which Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction(UUO)rats and the mechanism by which it ...OBJECTIVE:To elucidate the mechanism by which Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction(UUO)rats and the mechanism by which it reduces of renal fibrosis.METHODS:Male Wistar rats were randomly divided into 4 groups:the sham group,UUO group(180 d of left ureter ligation),UUO plus eplerenone(EPL)group,and UUO plus HJHR group.After 180 d of oral drug administration,blood and contralateral kidneys were collected for analysis.Angiogenesis-and fibrosis-related indexes were detected.RESULTS:HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels ofα-smooth muscle actin(α-SMA),vimentin and collagen I.Moreover,these treatments could reduce the expression of vascular endothelial growth factor-A(VEGFA)by inhibiting the infiltration of macrophages.Furthermore,HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production,which inhibited angiogenesis.Finally,the coexpressions of CD34,CD105 andα-SMA were decreased in the HJHR and EPL groups,indicating that endothelial-to-mesenchymal transition was inhibited.CONCLUSIONS:These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFAinduced angiogenesis,encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.展开更多
OBJECTIVE:To investigate the action and underlying mechanisms of Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)against unilateral ureteral obstruction(UUO)-induced injury in the contralateral kidney.METHODS:Forty-eigh...OBJECTIVE:To investigate the action and underlying mechanisms of Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)against unilateral ureteral obstruction(UUO)-induced injury in the contralateral kidney.METHODS:Forty-eight male Sprague-Dawley rats weighing(200±10)g were used in this study and randomly assigned to 4 groups:a sham group,a UUO group,a UUO+eplerenone(EPL)group,and a UUO+HJHR group.The contralateral kidneys were harvested for further study 180 d after surgery.Histological analysis,immunohistochemistry and immunofluorescence were used to study the fibrosis of the contralateral kidneys obtained from UUO rats.Contralateral kidney damagerelated pathway proteins were detected by real-time polymerase chain reaction and Western blot analysis.RESULTS:HJHR significantly inhibited fibrosis of the contralateral kidney in UUO rats by attenuating the UUOinduced macrophage-to-myofibroblast transition(MMT)in the contralateral kidney.Moreover,HJHR attenuated fibrosis in the contralateral kidney of UUO rats by preventing MMT through the aldosterone/mineralocorticoid receptor/serum/glucocorticoid regulated kinase 1 pathway.CONCLUSIONS:Our findings suggest that HJHR may be a potential treatment for renal interstitial fibrosis of obstructive nephropathy.展开更多
基金National Natural Science Foundation Project(No.81973780)。
文摘Objective:To explore the possible mechanism of Huoxue Yiqi recipe promoting angiogenesis by targeting VEGF with miR-484.Methods:The model of miR-484 overexpressed in HUVEC was prepared and intervened with Huoxue Yiqi Recipe Freeze-dried powder.The effects of Huoxue Yiqi Recipe on proliferation,migration and tubular forming ability of HUVEC were separatly detected by CCK-8 method,cell scratch test and Matrigel three-dimensional forming test in vitro.The effect of Huoxue Yiqi Recipe on VEGFA mRNA expression was detected by real-time fluorescence quantitative PCR.Results:Compared with the control group,the proliferation and migration area of cells in miR-484 overexpression model group decreased,the length,number of branches and nodes involved in tube formation decreased,the tube formation ability decreased significantly,and the expression level of VEGFA mRNA decreased,with statistical significance.Compared with the model group,the cell proliferation ability,migration area,length,number of branches and nodes involved in tube formation,tube formation ability and expression level of VEGFA mRNA in the Huoxue Yiqi Prescription group were up-regulated,and the difference was statistically significant(P<0.05).Conclusion:MiR-484 inhibits the expression of VEGFA and the proliferation,migration and formation of HUVEC,and Huoxue Yiqi recipe has a certain negative regulation effect on this process,which may be a new target of Huoxue Yiqi recipe to promote angiogenesis.
基金supported by the National Natural Science Foundation of China(No.30973833)
文摘Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation （D 15, D 18 and D21）. The rats were randomly assigned into 3 groups： normal group, model group [fetal growth restriction （FGR） model], and Bushen Tqi Huoxue （BYHR） recipe treatment group （BYHR group, the pregnant rats with FGR were treated with BYHR recipe）. Morphological analysis indicated that during initial villous formation, fetal nucle- ated erythrocytes （FNEs） appeared in maternal blood sinus （MBS）. Subsequently, FNEs were sur- rounded by endothelial cells to form fetal capillary （FC） and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining （EIS） in normal and BYHR groups. Whereas, villous formation was suppressed, normal in- crease in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flkl mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while de- creased on D21 in model group as compared with normal group and BYHR group. Immunohistochemi- cally, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D 15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.
基金Beijing Science and Technology Commission Project(No.131100002213006)National Natural Science Foundation of China General Project(Project Approval Number:81573958)
文摘Objective: To objectively evaluate the efficacy of Huoxue Tongluo Recipe(活血通络方) in the treatment of chemotherapy-induced peripheral neuropathy(CIPN).Methods: A multicenter, randomized, double-blind, block, and parallel-controlled study was conducted in which 184 subjects who met the inclusion criteria were randomized into a trial group(92 cases), a control group(46 cases), a placebo group(46 cases) at a 2:1:1 ratio, respectively.Huoxue Tongluo Recipe(活血通络方) granules, Huangqi Guizhi Wuwu Decoction(黄芪桂枝五物汤) instant granules, placebo instant granules were given for hand and foot soaking, with water temperature 38 ℃-45 ℃, soaking for 20 minutes and the intervention time was 14 days.Results:(1) The total effective test drug was 41.30%, the control group was 32.61%, and the placebo group was 32.61%.There was no significant difference in the efficiency of the 3 groups by CMH chi-square test(P>0.05);(2) In the statistics of previous chemotherapy regimens including oxaliplatin or paclitaxel as stratification factors, the overall efficiency of the trial group was significantly different from the other 2 groups.Conclusion: Huoxue Tongluo Recipe(活血通络方) external washing can improve the peripheral nerve injury caused by chemotherapy to some extent, especially in patients with previous chemotherapy regimen including oxaliplatin and paclitaxel.
基金funded by the Program of Shanghai Municipal Health Commission (No.19401970400)the National Natural Science Foundation of China (No.82174130 and No.82274262)Shanghai Collaborative Innovation Center of Industrial Transformation of Hospital TCM Preparation。
文摘Background:Hypertension,a prevalent disease,is a significant risk factor for coronary heart disease.Huoxue Qianyang Qutan Recipe (HQQR),a traditional Chinese herbal remedy,has been used for treating hypertension over several years.Objective:This study assesses HQQR’s efficacy for controlling blood pressure among patients with hypertension related to blood stasis,yang hyperactivity and phlegm.Design,setting,participants and interventions:A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,from July 2020 to June 2022.Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography.Participants aged18–80 years,exhibiting traditional Chinese medicine syndromes of blood stasis,yang hyperactivity or phlegm,along with grades 1 or 2 hypertension,were randomly categorized into two groups.The intervention group was given HQQR granules alongside conventional hypertension treatment,while the control group was given placebo granules in addition to conventional treatment for 12 weeks.Main outcome measures:The primary outcome was clinic blood pressure,whereas secondary outcomes included metabolic indices (e.g.,homeostasis model assessment of insulin resistance[HOMA-IR],total cholesterol[TC],low-density lipoprotein cholesterol and triglyceride),target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio[UACR]) and inflammation indices(interleukin-6[IL-6]and high-sensitivity C-reactive protein[hs-CRP]).Results:HQQR’s primary components were identified as salvianolic acid B,emodin and ferulic acid.Of the 216 participants (108 in each group),compared to the control,the intervention group exhibited significant improvements (P<0.001) in clinic systolic blood pressure ([136.24±7.63]vs[130.06±8.50]mmHg),clinic diastolic blood pressure ([84.34±8.72]vs[80.46±6.05]mmHg),home systolic blood pressure([131.64±8.74]vs[122.36±8.45]mmHg) and home diastolic blood pressure ([78.47±9.53]vs[71.79±6.82]mm Hg).HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure:[133.75±10.49]vs[132.46±8.84]mmHg and 24-hour diastolic blood pressure:[84.12±8.01]vs[82.11±7.45]mmHg) and an improvement in HOMA-IR ([4.09±1.72]vs[3.98±1.44]),TC ([4.66±1.47]vs[3.75±1.81]mmol/L) and UACR (75.94[5.12,401.12]vs 45.61[4.26,234.26]).Moreover,HQQR demonstrated a decrease in hs-CRP (1.46[0.10,10.53]vs 0.57[0.12,3.99]mg/L) and IL-6 (6.69[2.00,29.74]vs 5.27[2.00,9.73]pg/mL),with no reported side effects (P<0.001).Conclusion:This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure,glycolipid metabolism,and inflammation in patients with hypertension.
基金Natural Science Foundation-funded Project:Effect of Macrophage-to-Myofibroblast Transition in Contralateral Kidney of Unilateral Ureteral Obstruction Rats Through the Aldosterone/MR/SGK1 Pathway and Inhibition of Chinese Herbs(No.81873251)Natural Science Foundation-funded Project:Aldosterone Stimulates MR Activation to Induce Lymphangiogenesis in the Contralateral Kidney of UUO Rats and the Protective Effect of Yiqi Jiedu Huayu Herbs(No.82174317)+1 种基金Hebei Provincial Postgraduate Innovative Ability Cultivation Funding Project:Aldosterone Induced Macrophages to Secrete VEGFA to Participate in Renal Angiogenesis and the Protective Effect of Huoxue Jiedu Huayu Recipe(CXZZBS2023140)Construction Program of New Research and Development Platform and Institution,Hebei Province Innovation Ability Promotion Plan under Grant No.20567624H。
文摘OBJECTIVE:To elucidate the mechanism by which Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction(UUO)rats and the mechanism by which it reduces of renal fibrosis.METHODS:Male Wistar rats were randomly divided into 4 groups:the sham group,UUO group(180 d of left ureter ligation),UUO plus eplerenone(EPL)group,and UUO plus HJHR group.After 180 d of oral drug administration,blood and contralateral kidneys were collected for analysis.Angiogenesis-and fibrosis-related indexes were detected.RESULTS:HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels ofα-smooth muscle actin(α-SMA),vimentin and collagen I.Moreover,these treatments could reduce the expression of vascular endothelial growth factor-A(VEGFA)by inhibiting the infiltration of macrophages.Furthermore,HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production,which inhibited angiogenesis.Finally,the coexpressions of CD34,CD105 andα-SMA were decreased in the HJHR and EPL groups,indicating that endothelial-to-mesenchymal transition was inhibited.CONCLUSIONS:These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFAinduced angiogenesis,encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.
基金Supported by Natural Science Foundation-funded Project:Effect of Macrophage-to-Myofibroblast Transition in Contralateral Kidney of Unilateral Ureteral Obstruction Rats Through the Aldosterone/MR/SGK1 Pathway and Inhibition of Chinese Herbs(No.81873251)Natural Science Foundation-funded Project:Aldosterone-induced Macrophage Polarization-lymphatic Endothelial Cell-like Transformation Involved in Renal Fibrosis and the Protective Effect of Yiqi Jiedu Huayu Herbs(No.82205006)Youth Top Talent Project of Hebei Provincial Department of Education:Mechanism of Renal Fibrosis Induced by NF-kB/IL-8 Induced MMT in UUO Rats(BJK2022004)。
文摘OBJECTIVE:To investigate the action and underlying mechanisms of Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)against unilateral ureteral obstruction(UUO)-induced injury in the contralateral kidney.METHODS:Forty-eight male Sprague-Dawley rats weighing(200±10)g were used in this study and randomly assigned to 4 groups:a sham group,a UUO group,a UUO+eplerenone(EPL)group,and a UUO+HJHR group.The contralateral kidneys were harvested for further study 180 d after surgery.Histological analysis,immunohistochemistry and immunofluorescence were used to study the fibrosis of the contralateral kidneys obtained from UUO rats.Contralateral kidney damagerelated pathway proteins were detected by real-time polymerase chain reaction and Western blot analysis.RESULTS:HJHR significantly inhibited fibrosis of the contralateral kidney in UUO rats by attenuating the UUOinduced macrophage-to-myofibroblast transition(MMT)in the contralateral kidney.Moreover,HJHR attenuated fibrosis in the contralateral kidney of UUO rats by preventing MMT through the aldosterone/mineralocorticoid receptor/serum/glucocorticoid regulated kinase 1 pathway.CONCLUSIONS:Our findings suggest that HJHR may be a potential treatment for renal interstitial fibrosis of obstructive nephropathy.
