OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans ; Microcirculation/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Stomach Neoplasms/physiopathology* ; Emulsions ; Male ; Plant Oils/administration & dosage* ; Brucea/chemistry* ; Middle Aged ; Female ; Drug Combinations ; Human Umbilical Vein Endothelial Cells/metabolism* ; Seeds/chemistry* ; Injections ; Vascular Endothelial Growth Factor A/metabolism* ; Aged ; Network Pharmacology

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

OBJECTIVE: This study demonstrated that dexamethasone (DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α (TNF-α) during severe acute pancreatitis (SAP), and improves the renal microcirculation. METHODS: Ninety mice were evenly divided into 3 groups (Sham, SAP, and SAP+DEX). The SAP mice model was established by ligature of pancreatic duct and intraperitoneal injection of cerulein. Renal perfusion and function, and morphological changes of the glycocalyx were evaluated by laser Doppler velocimetry, electron microscopy, and histopathology (hematoxylin and eosin (H&E) staining), respectively. Serum levels of syndecan-1 and TNF-α were assessed by enzyme-linked immunosorbent assay (ELISA). The protective effects of dexamethasone on the glycocalyx and renal microcirculation were evaluated. RESULTS: Significantly high levels of serum TNF-α were detected 3 h after the onset of SAP. These levels might induce degradation of the glycocalyx and kidney hypoperfusion, resulting in kidney microcirculation dysfunction. The application of dexamethasone reduced the degradation of the glycocalyx and improved perfusion of kidney. CONCLUSIONS Dexamethasone protects the endothelial glycocalyx from inflammatory degradation possibly initiated by TNF-α during SAP. This is might be a significant discovery that helps to prevent tissue edema and hypoperfusion in the future.
Acute Disease ; Animals ; Dexamethasone/pharmacology* ; Disease Models, Animal ; Edema/metabolism* ; Endothelium, Vascular/metabolism* ; Enzyme-Linked Immunosorbent Assay ; Glycocalyx/drug effects* ; Kidney/drug effects* ; Male ; Mice ; Mice, Inbred C57BL ; Microcirculation ; Pancreatitis/drug therapy* ; Perfusion ; Protective Agents/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVE: To investigate the effects of Coriaria Sinica Maxim's extract(CSME) on microcirculation and oxidative stress of wounds in rats with deep second-degree burn. METHODS: One hundred and eighty rats were randomly divided into normal saline group(NS), white petroleum group(WPL), silver sulfadiazine group (SSD), Coriariasinica Maxim's extract group which were divided into low dose(CSME-L),middle dose(CSME-M) and high dose(CSME-H). After anesthesia with burn instrument to burn the hair removal area of rats, these wounds were confirmed by pathological results with deep second degree burns.And then,those drugs were applied respectively on the wounds,such as NS、WPL、SSD and different concentrations of CSME. After injury at 48 h, 7 d, 14 d and 21 d,the healing rate(HR) of wound was measured, and the microvessel density (MVD), tissue moisture (TM), vascular endothelial growth factor (VEGF), model driven architecture (MDA), superoxide dismutase(SOD) and hydroxyproline(HYP) were detected, too. All pathological sections of the wound tissue were observed. RESULTS: The HR of CSME groups were obviously increased with a dose-dependent manner, which was significantly higher than that of NS and WPL (<0.05); On the 21 day, the diameter, number, distribution of the vessels and and the TM were less than other groups with a dose-dependent manner; On the 7 and 14 day after injury, CSME groups were significantly higher than the NS, WPL and SSD with a dose-dependent manner (<0.05), but, on the 21 day after injury, they were lower than NS, WPL and SSD with a dose-dependent (<0.05) manner. The levels of SOD, HYP, NO and ET in CSME groups were higher than those in other groups with dose-dependent on SOD activity, HYP, NO and ET content (<0.05), while MDA activity was weaker than other groups (<0.05). Similarly, pathological findings were also shown that CSME groups were better than other groups with a dose-dependent manner in decrease decreasing of wound repair time and hyperplasia of scar tissue. CONCLUSIONS CSME can relieve tissue edema, promote wound contraction, speed up the formation of eschar and accelerate the proliferation of granulation tissue, which are beneficial to the wound healing in the early stages. But, it can inhibit the hyperplasia of granulation tissue to prevent the excessive scar hyperplasia of burn wound in the later stages. Its mechanism is related to regulation what microcirculation, oxidativestress, NO and VEGF.
Animals ; Burns ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Hydroxyproline ; metabolism ; Malondialdehyde ; metabolism ; Microcirculation ; Oxidative Stress ; Random Allocation ; Rats ; Superoxide Dismutase ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Wound Healing ; drug effects

OBJECTIVETo examine whether sodium tanshinone II A sulfonate (STS), the main effective component of Salvia miltiorrhiza is effective in relieving the microcirculatory disturbance of small intestine by suppressing the production of reactive oxygen species (ROS) in rats with sepsis.

METHODSA rat model of sepsis was induced by cecal ligation and puncture (CLP). Rats (n =40) were randomly divided into 4 groups: sham-operated group (sham, n =10), sepsis group (CLP, n =10), STS treatment group (STS, n =10) and ROS scavenger dimethylthiourea (DMTU, n =10) group. Animals in the STS group were injected with STS (1 mg/kg) for 10 min through the right external jugular vein after the CLP operation, and animals in the CLP group were given the same volume of normal saline after the CLP operation. Animals in the DMTU group were intraperitoneally injected with 5 mL/kg of 20% DMTU 1 h before CLP. The histopathologic changes in the intestinal tissues and changes of mesenteric microcirculation were observed. The levels of ROS in intestinal tissues from each group were qualitatively evaluated using a fluorescent microscope. The expressions of apoptosis signal-regulating kinase (ASK1), phosphorylated ASK1 (phospho-ASK1), p38 mitogen-activated protein kinases (p38 MAPK), phosphorylated p38 MAPK (phospho-p38 MAPK) and tissue factor (TF) were determined by Western blotting.

RESULTSIt was shown that there were obvious microcirculatory disturbance (P <0.05) and tissue injuries in intestinal tissues after CLP operation. The levels of ROS production, phospho-ASK1, phospho-p38 MAPK and TF were increased. Both STS and DMTU suppressed ROS, phospho-ASK1, phospho-p38 MAPK and TF production, and ameliorated the microcirculatory disturbance and tissues injury (P <0.01).

CONCLUSIONSTS can ameliorate the microcirculatory disturbance of the small intestine by attenuating the production of ROS in rats with sepsis.

Animals ; Intestine, Small ; blood supply ; drug effects ; pathology ; MAP Kinase Kinase Kinase 5 ; metabolism ; Male ; Microcirculation ; drug effects ; Phenanthrenes ; chemistry ; pharmacology ; therapeutic use ; Phosphorylation ; drug effects ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Sepsis ; drug therapy ; enzymology ; pathology ; physiopathology ; Thromboplastin ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

PURPOSETo investigate the effects of salvianolic acid B (SAB) on tumor necrosis factor a (TNF-α) induced alterations of cerebral microcirculation with a bone-abrading model.

METHODSThe influences of craniotomy model and bone-abrading model on cerebral microcirculation were compared. The bone-abrading method was used to detect the effects of intracerebroventricular application of 40 μg/kg·bw TNF-α on cerebral venular leakage of fluorescein isothiocyanate (FITC)- albulmin and the rolling and adhesion of leukocytes on venules with fluorescence tracer rhodamine 6G. The therapeutical effects of SAB on TNF-α induced microcirculatory alteration were observed, with continuous intravenous injection of 5 mg/kg·h SAB starting at 20 min before or 20 min after TNF-α administration, respectively. The expressions of CD11b/CD18 and CD62L in leukocytes were measured with flow cytometry. Immunohistochemical staining was also used to detect E-selectin and ICAM-1 expression in endothelial cells.

RESULTSCompared with craniotomy method, the bone-abrading method preserved a higher erythrocyte velocity in cerebral venules and more opening capillaries. TNF-α intervention only caused responses of vascular hyperpermeability and leukocyte rolling on venular walls, without leukocyte adhesion and other hemodynamic changes. Pre- or post-SAB treatment attenuated those responses and suppressed the enhanced expressions of CD11b/CD18 and CD62L in leukocytes and E-selectin and ICAM-1 in endothelial cells induced by TNF-α.

CONCLUSIONSThe pre- and post-applications of SAB during TNF-α stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling.

Animals ; Benzofurans ; pharmacology ; Blood Flow Velocity ; Cerebrovascular Circulation ; drug effects ; Craniotomy ; Disease Models, Animal ; E-Selectin ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Mice ; Mice, Inbred C57BL ; Microcirculation ; drug effects ; Random Allocation ; Reference Values ; Tumor Necrosis Factor-alpha ; administration & dosage

OBJECTIVETo investigate the effects of dexmedetomidine on renal microcirculatory perfusion in rabbits with renal ischemia/reperfusion (I/R) injury rabbit by quantitative analysis of contrast-enhanced ultrasound (CEUS).

METHODSTwenty- four New Zealand rabbits were randomly divided into 3 groups (8 in each), including a control group, renal I/R injury group and dexmedetomidine group. In the latter two groups, the right kidney of the rabbits was resected and I/R injury was induced in the left kidney. In dexmedetomidine group, the rabbits received an intraperitoneal dose of 10 µg/kg dexmedetomidine 30 min before renal ischemia, and 24 h after reperfusion, the renal size and renal artery resistance (RI) were measured, and renal cortex perfusion was observed by CEUS. The time-to-peak intensity (TTP), peak signal intensity (PSI), gradient between start frame to peak frame (Grad) and area under the curve (AUC) were quantitatively analyzed using the time-intensity curves. Pathological changes of the kidney were also observed.

RESULTSCompared with the control group, the rabbits in I/R and dexmedetomidine groups showed distinct changes of the renal size with obvious renal pathologies. RI, PPT and AUC all increased, and PSI and Grad decreased significantly in I/R and dexmedetomidine groups (P<0.05). Compared with I/R group, obvious improvement of the renal size and renal pathologies were observed in dexmedetomidine group, which showed significantly decreased RI, PPT and AUC and increased PSI and Grad (P<0.05).

CONCLUSIONCEUS combined with the time-intensity curve parameters allows quantitative and dynamic analysis of the protective effects of dexmedetomidine on microcirculatory perfusion in rabbits with renal I/R injury.

Animals ; Dexmedetomidine ; pharmacology ; Disease Models, Animal ; Kidney ; blood supply ; drug effects ; Kidney Diseases ; drug therapy ; Microcirculation ; drug effects ; Rabbits ; Renal Artery ; drug effects ; Reperfusion Injury ; drug therapy

Pathological angiogenesis of liver which includes liver sinusoidal capillarization due to lose of fenestraes of liver sinusoidal endothelial cells (LSECs) and formation of new vascular, is a crucial mechanism responsible for origination and development of liver fifibrosis and closely involves in the development of cirrhosis and hepatic cancer. Anti-neovascularization medicine such as sorafenib can decrease portosystemic shunts, improve splanchnic hyperdynamic circulation, lower portal hypertension, while it can not be applied in clinic due to its serious toxic and side reactions. Chinese herbal formula can effectively inhibit pathological angiogenesis of liver, improve microcirculation of liver, and decrease the probability of gastrointestinal hemorrhage in cirrhotic patients. Different Chinese herbal formula are of different characteristics on inhibiting pathological angiogenesis in liver fifibrosis, which partly explains synergistic effect of different compatibility of Chinese materia medica and opens up good vista for Chinese medicine against liver fifibrosis through inhibiting angiogenesis.
Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Esophageal and Gastric Varices ; complications ; drug therapy ; Hemorrhage ; complications ; drug therapy ; Humans ; Liver Cirrhosis ; complications ; drug therapy ; Microcirculation ; drug effects ; Neovascularization, Pathologic ; complications ; drug therapy

BACKGROUNDSeveral studies have demonstrated that primary percutaneous coronary intervention (PCI) can result in reperfusion injury. This study aims to investigate the effectiveness of liposomal prostaglandin E1 (Lipo-PGE1, Alprostadil, Beijing Tide Pharmaceutical Co., Ltd.) for enhancing microcirculation in reperfusion injury. In addition, this study determined the optimal administration method for acute ST elevation myocardial infarction (STEMI) patients undergoing primary PCI.

METHODSTotally, 68 patients with STEMI were randomly assigned to two groups: intravenous administration of Lipo-PGE1 (Group A), and no Lipo-PGE1 administration (Group B). The corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC) and myocardial blush grade (MBG) were calculated. Patients were followed up for 6 months. Major adverse cardiac events (MACE) were also measured.

RESULTSThere was no significant difference in the baseline characteristics between the two groups. The cTFC parameter in Group A was significantly lower than Group B (18.06 ± 2.06 vs. 25.31 ± 2.59, P < 0.01). The ratio of final MBG grade-3 was significantly higher (P < 0.05) in Group A (87.9%) relative to Group B (65.7%). There was no significant difference between the two groups in final TIMI-3 flow and no-reflow. Patients were followed up for 6 months, and the occurrence of MACE in Group A was significantly lower than that in Group B (6.1% vs. 25.9% respectively, P < 0.05).

CONCLUSIONSMyocardial microcirculation of reperfusion injury in patients with STEMI, after primary PCI, can be improved by administering Lipo-PGE1.

Administration, Intravenous ; Aged ; Alprostadil ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Microcirculation ; drug effects ; Middle Aged ; Myocardial Infarction ; drug therapy ; Percutaneous Coronary Intervention ; methods