1.Naloxone can reverse blunted baroreflex sensitivity after acute myocardial infarction
Ben HE ; Daosheng ZHENG ; Yixian WU
Chinese Pharmacological Bulletin 1987;0(02):-
Acute myocardial infarction (AMI) model was made in SD rats by coronary ligation, the effects of naloxone (Nal) on the baroreflex sensitivity (BRS) were evaluated by administrated Nal intravenously (iv) and in-tracisternally (ic) before and after 1 h of AMI.Results showed that both pre and post AMI can Nal potentiate the BRS whether iv or ic. These results indicate that Nal may reverse the blunted BRS after AMI.
2.Inhibitory effect of cholecystokinin octapeptide on carotid sinus nerve afferent discharge in anesthetized rats
Yixian LIU ; Hao ZHANG ; Jinghui DONG ; Qian LI ; Ruirong HE
Chinese Journal of Pharmacology and Toxicology 2005;19(1):18-23
AIM To study if cholecystokinin octapeptide (CCK-8) alter cardiovascular functions by its direct inhibitory effect on carotid sinus baroreceptor (CSB) activity. METHODS The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. RESULTS ① CCK-8 0.1, 0.5 and 1.0 μmol·L-1 shifted FCCB to the right and downward, with a marked decrease in peak slope and peak integral value of carotid sinus nerve discharge in a concentration-dependent manner, indicating the inhibitory effect of CCK-8 on CSB activity. ② Pretreatment with proglumide (100 μmol·L-1), a nonselective CCK receptor antagonist, or Bay K8644 (0.5 μmol·L-1), an agonist of calcium channel, partially attenuated the inhibitory effect of CCK-8 (0.5 μmol·L-1) on CSB activity. Pretreatment with L-NAME (100 μmol·L-1), an inhibitor of NO synthase, did not affect the inhibitory action of CCK-8. CONCLUSION CCK-8 inhibits CSB activity, which may be mediated by activating CCK receptors in the carotid sinus area and thereby resulting in an inhibition of stretch-sensitive channels and decrease in Ca2+ influx.
3.The clinical value of neutrophil to lymphocyte ratio in postmenopausal patients with type 2 diabetes
Yixian PENG ; Yin YANG ; Wengao LI ; Zhiyong WU ; Peng LUO ; Ru TANG ; Lei HE
Tianjin Medical Journal 2017;45(1):68-71
Objective To investigate the clinical value of neutrophil-lymphocyte ratio (NLR) in postmenopausal patients with type 2 diabetes mellitus (T2DM). Methods A total of 128 newly diagnosed T2DM female patients were randomly recruited from the Zhujiang Hospital of Southern Medical University from March to September 2015. According to the physiological state, the patients were divided into menopausal group (n=66) and non-menopausal group (n=62). Fifty-six healthy females were chosen as the control group. The values of blood pressure, blood lipid, fasting plasma glucose (FPG), fasting insulin (FINS) and white blood count (WBC), neutrophil count, percentage of neutrophils,lymphocytes count, and percentage of lymphocytes were detected and compared between three groups. The NLR and the HOMA insulin resistance index (HOMA-IR) were calculated. Results Age, systolic blood pressure (SBP), triglyceride (TG), FINS, percentage of neutrophil, NLR, HOMA-IR were significantly higher in menopause group than those of control group and non-menopause group (P<0.05). There were no significant differences in diastolic blood pressure (DBP) and FPG between menopause group and non-menopause group, but both were significantly higher than those of control group (P < 0.05). There were no significant differences in total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), WBC and HbA1c between three groups (P>0.05). There was no linear correlation between NLR and HOMA-IR (rs=0.015, P > 0.05), HbA1c (r=0.030, P > 0.05). Conclusion NLR is of a certain significance in the assessment of inflammatory status and IR levels in postmenopausal women with T2DM, which may be related to the changes of autonomic nervous system.
4.Inhibition of rhynchophylline on carotid sinus baroreceptor activity in anesthetized rats
Yixian LIU ; Jinghui DONG ; Lu GAO ; Huijuan MA ; Yuming WU ; Yi ZHANG ; Ruirong HE
Chinese Journal of Pharmacology and Toxicology 2009;23(3):161-167
AIM To elucidate the effect of rhynchophylline(Rhy) on carotid sinus baroreceptor activity (CBA). METHODS By recording sinus nerve afferent discharge activity with isolated carotid sinus perfusion, parameters of CBA, such as peak slope (PS), peak integral value (PIV), threshold pressure (TP) and saturation pressure (SP) were examined. ①Rhy 10, 50, and 100 μmol·L-1, dissolved in K-H solution, was perfused into isolated carotid sinus, then the effects of Rhy on parameters of CBA were observed while intrasinus pressure was altered in a stepwise manner. ②NG-nitro-L-arginine methyl ester (L-NAME) 10 mmol·L-1, tetraethylammonium (TEA) 1 mmol·L-1 and Bay K8644 500 nmol·L-1 were perfused into isolated carotid sinus, and effects of them on the response of carotid baroreceptor to Rhy were observed. RESULTS ① By perfusing the isolated carotid sinus with Rhy 10 μmol·L-1, PS decreased from (19.2±0.3)% to (18.2±0.1)%·kPa-1and the PIV decreased from (219.3±3.3)% to (199.1±3.8)%, while TP and SP increased from (8.2±0.3) to (9.1±0.1)kPa and (21.5±0.1) to (22.1±0.1)kPa, respectively. By perfusing with Rhy 50 and 100 μmol·L-1, the changes in PS, TP and SP were in concentration-dependent manner, and this indicated inhibitory effect of Rhy on CBA. ②Pretreatment with L-NAME 100 μmol·L-1 did not affect inhibitory action of Rhy 50 μmol·L-1 on CBA. ③Pretreatment with TEA 1 mmol·L-1 had no effect on inhibitory effect of Rhy 50 μmol·L-1 on CBA. ④Pretreatment with Bay K8644 500 nmol·L-1 could mostly attenuate effect of Rhy 50 μmol·L-1 on CBA. CONCLUSION Rhy inhibits CBA via blocking calcium influx in baroreceptor nerve ending.
5.The relationship between hyperuricemia with neutrophil-to-lymphocyte ratio and insulin resistance in type ;2 diabetes mellitus
Yihua HUANG ; Peng LUO ; Siyuan YU ; Ru TANG ; Yixian PENG ; Lei HE
The Journal of Practical Medicine 2016;32(5):731-734,735
Objective To research the relationship between Serum uric acid (SUA) levels and the Neu-trophil-to-lymphocyte Ratio (NLR) of Type 2 Diabetes Mellitus (T2DM) patients. Method 273 newly diag-nosed T2DM patients are selected in accordance with the WHO diagnostic criteria: Male subjects with SUA lev-els ≥ 416 μmol/L(70 mg/L), and female subjects with SUA levels ≥ 357 μmol/L (60 mg/L) are sorted into the high SUA (HUA) group (224 subjects), and the rest into the normal SUA (NUA) group (49 subjects). 100 subjects were selected as a control group. One-Way analysis of variance was applied to the data of the three groups; Pearson correlation analysis was used to calculate the correlation of SUA levels , NLR and IR; risk fac-tors influencing SUA levels were analyzed with Logistic regression analysis; ROC curve analysis was used to de-termine the diagnostic value of NLR to HUA, and the optimal threshold value of NLR. Result (1) The NLR and IR of the HUA group was significantly higher than those of the NUA group (2.54 ± 0.63 vs. 2.05 ± 0.61, P < 0.001; 3.70 ± 1.86 vs. 2.71 ± 1.43, P < 0.001); (2) In the HUA group, UA was positively correlated with NLR and IR (respectively r = 0.480, P < 0.001; r = 0.332, P < 0.001). (3)NLR (P < 0.001, EXP(B)= 8.045, 95%CI = 4.597 ~ 14.079) was a risk factor of Hyperuricemia. Conclusion Our results suggest that NLR may be an independent risk factor of Hyperuricemia.
6.Research progress on aspiration in patients with dysphagia after ischemic stroke
Yixian HE ; Gao LIU ; Lu ZHOU ; Muwei YANG ; Qingyuan GUO ; Enli CAI
Chinese Journal of Primary Medicine and Pharmacy 2023;30(4):631-634
Based on the research results of aspiration in patients with dysphagia after ischemic stroke at home and abroad, this paper reviews the definition, detection methods, and risk factors of aspiration and emphasizes the incidence rate and severity of this disease. The authors conclude that preventing aspiration can decrease the incidence rate of aspiration pneumonia, change the clinical outcome of patients, and thereby save medical resources.
7.Correlation between white matter hyperintensities and the outcomes after reperfusion therapy in patients with acute ischemic stroke
Qijing WANG ; Yixian LIU ; Jing ZENG ; Xingchen LIU ; Feng WANG ; Yufeng HE ; Sisi XU ; Benguo WANG
International Journal of Cerebrovascular Diseases 2021;29(11):812-819
Objective:To investigate the correlation between white matter hyperintensities (WMHs) and the outcomes after reperfusion therapy in patients with acute ischemic stroke (AIS).Methods:Patients with AIS treated with reperfusion therapy (intravenous thrombolysis, endovascular mechanical thrombectomy or bridging therapy) in the Stroke Center of Zhongshan Hospital of traditional Chinese Medicine from January 2014 to December 2019 were retrospectively enrolled. The clinical baseline data of the patients were collected. The Fazekas scale was used to evaluate the severity of WMHs according to the MRI images. At 90 d after discharge, the modified Rankin Scale was used to evaluate the outcomes. A score of ≤ 2 was defined as good outcome, and a score of >2 was defined as poor outcome. Binary multivariate logistic regression analysis was used to determine the independent risk factors for hemorrhagic transformation (HT), symptomatic intracranial hemorrhage (sICH), and poor outcomes. Results:A total of 676 patients with AIS treated with reperfusion therapy were enrolled. Among them, 506 patients (74.9%) were complicated with WMHs, and 80 (11.8%) had severe WMHs. One hundred and thirty-two patients (19.5%) had HT, 34 (5.0%) had sICH, and 306 (45.3%) had a poor outcome. Multivariate logistic regression analysis showed that severe WMHs was an independent risk factor for the occurrence of HT (odds ratio [ OR] 1.890, 95% confidence interval [ CI] 1.047-3.413; P=0.035) and poor outcomes ( OR 3.366, 95% CI 1.567-7.232; P=0.002) after reperfusion treatment in patients with AIS, but there was no independent correlation with sICH ( OR 8.403, 95% CI 0.891-79.294; P=0.063). Conclusion:Severe WMHs is an independent risk factor for the occurrence of HT and poor outcomes in patients with AIS after reperfusion treatment, but it has no independent correlation with sICH.
8.Effect of collateral circulation on hemorrhagic transformation or short-term prognoses in patients with acute ischemia stroke after different reperfusion therapies
Yixian LIU ; Qijing WANG ; Xingchen LIU ; Yufeng HE ; Feng WANG ; Sisi XU ; Benguo WANG
Chinese Journal of Neuromedicine 2021;20(11):1108-1116
Objective:To investigate the correlations of collateral circulation with hemorrhagic transformation (HT) and short-term prognoses in patients with acute ischemic stroke (AIS) after different reperfusion therapies.Methods:Four hundred and forty-nine patients with AIS after different reperfusion therapies, admitted to our hospital from January 2016 to December 2019, were chosen in our study. These patients were divided into HT group ( n=90) and non-HT group ( n=359) according to whether HT presented or not. The baseline data, clinical characteristics, and prognoses of patients between the 2 groups were compared. And the variables of P<0.05 in univariate analysis were re-analyzed by multivariate Logistics regression to identify the independent influencing factors for HT in patients with AIS; the correlations between cerebral collateral circulation grading (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [ASITN/SIR], and modified Thrombolysis in Cerebral Infarction [mTICI]) and modified Rankin scale (mRS) scores at discharge were explored. Results:(1) There were significant differences between patients in the two groups in terms of age, percentages of patients with atrial fibrillation, baseline National Institutes of Health Stroke Scale (NIHSS) scores, emergency blood glucose, platelet count, and percentages of patients used dual antiplatelet agents and statin ( P<0.05). (2) Results of multivariate Logistics analysis: moderate stroke (NIHSS scores of 9-15), severe stroke (NIHSS scores≥16), elevated emergency glucose, atherosclerotic cerebral infarction and bridging therapy were independent risk factors for HT, and good collateral circulation status and dual antiplatelet therapy were independent protective factors for HT. (3) Correlation of collateral circulation with short-term prognosis: mRS scores of patients at discharge were negatively correlated with ASITN/SIR grading of collateral circulation and mTICI grading ( rs=-0.201, P=0.003; rs=-0.222, P=0.001). Further grouping by different reperfusion therapies showed that ASITN/SIR grading in the intravenous thrombolysis group and mTICI grading in the bridging therapy group were negatively correlated with mRS scores of these patients at discharge ( rs=-0.176, P=0.016; rs=-0.271, P=0.010). Conclusion:AIS patients with poor collateral circulation who receive reperfusion therapies are more likely to develop HT than patients with good collateral circulation, enjoying a relatively poor short-term prognosis.
9.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
10.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.