1.Research advances of M3 receptor: a new target for treating and preventing cardiovascular disease.
Yan LIU ; Yanjie Lü ; Baofeng YANG
Acta Pharmaceutica Sinica 2015;50(4):393-9
Cardiovascular disease, with high morbidity and mortality, has been threatening the health of human beings. Therefore, expecting to find a more effective therapeutic method, a plenty of researchers devote themselves to the study of the cardiovascular disease all the time. Since discovered on the heart, M3 receptor of muscarinic acetylcholine receptor (mAchR, M receptor) became a new starting point of the research of the cardiovascular disease. With more and more investigation, many people found that M3 receptor could protect the heart from kinds of cardiovascular disease, which may make it a new hopeful therapeutic point. So, expecting to give support to the reference and encouragement for the study of disease related to M3 receptor in future, this review expounds M3 receptor on the heart from the main following aspects: the effect on the heart, the influence on the cardiovascular disease and the mechanism of M3 receptor involved.
2.Efficacy analysis of selective posterior rhizotomy at medullary conus for treatment of double lower extremities spastic cerebral palsy
Baofeng YAN ; Xinping LUAN ; Xia LU ; Bin LI
Chinese Journal of Applied Clinical Pediatrics 2016;31(23):1813-1816
Objective To investigate the clinical efficacy of L1 -S1 selective posterior rhizotomy (SPR)at the medullary conus level for the treatment of double lower extremities spastic cerebral palsy(CP).Methods A total of 1 09 double lower extremities spastic CP children underwent SPR at the level of medullary consul were selected in the Second Affiliated Hospital of Xinjiang Medical University from October 201 0 to May 201 4.The 4 groups were analyzed in terms of muscle tension and gross motor function of the lower limbs 6 months before and after operation,retrospective-ly.The SPSS 1 7.0 software was used for statistical analysis.Results Patients had different degrees of improvement in gross motor function and reduction of spasticity in all muscle groups of lower limbs after operation.Six months after the operation,the muscular tension of hip flexor,hip adductor,knee flexor and plantar flexors (modified Ashworth spastic scale score)were all improved compared with preoperation (t =1 6.635,27.41 1 ,31 .362,38.81 9,all P <0.01 ).Gross motor function of lower limbs (Gross Motor Function Measure)at 6 months after the operation was significantly im-proved compared with preoperation (51 .97 ±1 2.92 vs 41 .01 ±1 1 .46),and the difference was significant(t =26.67, P <0.01 ).The postoperative complications:intracranial hypotension headache (5 cases,4.59%),postoperative high fever (2 cases,1 .83%),incision fat liquefaction (2 cases,1 .83%),sensory barriers of lower limbs (1 case, 0.92%),and urine obstacles (1 case,0.92%).Conclusions SPR at the level of medullary conus has the advantages of minimal injury,rapid recovery and little influence on the stability of the spine.In addition,the procedure can relieve the spasticity of lower limbs of the CP patients effectively.
3.Progress in the treatment of diabetic wound healing via stem cells transplant.
Qingxin CAI ; Lu WANG ; Yan ZHANG ; Baofeng YANG
Acta Pharmaceutica Sinica 2015;50(1):1-6
The morbidity of diabetes has been increasing rapidly in recent years. Delayed wound healing has become a common complication in diabetes, which seriously affects the orthobiosis of patients. Exploring and finding the molecular mechanisms of diabetic wound healing and the effective therapies to promote wound healing have important clinical significances. Stem cells transplant has become a research hotspot in accelerating diabetic wound healing. This article reviewed the present approaches concerning stem cells transplant in diabetic wound healing both at domestic and abroad, and looked forward the clinical therapy of stem cells on diabetic wound healing.
4.CARDIAC-HEMODYNAMIC EFFECTS OF M3 RECEPTOR AGONIST ON RAT AND RABBIT HEARTS
Yan LIU ; Yue WANG ; Manling MA ; Yan ZHANG ; Houwei LI ; Qingwen CHEN ; Baofeng YANG
Acta Pharmaceutica Sinica 2001;36(2):84-87
AIM To study the activation of choline on M3-R in heart and observe the hemodynamic changes of rat and rabbit. METHODS A cardiac catheter was inserted into the left ventricular cavity via the right carotid artery, then the HR, LVSP, LVEDP, and ±dp/dt were measured using a polygraph system. RESULTS Choline was shown to decrease the hemodynamic assessments, such as HR, +dp/dt, LVSP and LVEDP. while the M3-R antagonist 4-DAMP (4-diphenylacetoxy-N-methylpiperidine-methiodide) showed little effect on these assessments. It was found to reverse the hemodynamic effects of choline. CONCLUSION M3 receptor agonist can produce negative inotropic and chronotropic effects on the heart of rat and rabbit.
5.Effects of chlorzoxazone on HepG2 tumor cells
Changlong FAN ; Yan LUAN ; Yan CHEN ; Jun ZHANG ; Wan ZHANG ; Baofeng YANG ; Deli DONG
Chinese Pharmacological Bulletin 2003;0(09):-
Aim To investigate effects of chlorzoxazone on survival and apoptosis of HepG2 cells.Methods The necrosis of HepG2 cells was evaluated by measurement of LDH release.The effects of chlorzoxazone on survival of HepG2 cells were assayed by MTT dyereduction.The effects of chlorzoxazone on cell apoptosis was analyzed by TUNEL method.The ultrastructure of HepG2 cells was observed by transmission electron microscope.Results Chlorzoxazone at concentrations of 100~500 ?mol?L-1 inhibited survival ratios of HepG2 cells in a dose-dependent manner significantly.Typical apoptotic changes were observed in HepG2 cells under the fluorescence microscope and transmission electron microscope.Apoptosis of HepG2 cells was induced after treatment of chlorzoxazone at concentrations from 100 ?mol?L-1 to 500 ?mol?L-1 for 48h,which showed obvious concentration-effect relationship.The apoptotic ratios of HepG2 cells were also increased when chlorzoxazone(100,200,300 and 500 ?mol?L-1) was treated for 24,48 and 72 h,which showed obvious time-effect relationship.Conclusion Chlorzoxazone inhibited HepG2 cells survival and induced cell apoptosis.
6.Actigraph monitor in quantitative evaluation of severity of movement disorders
Yan SUN ; Weidong PAN ; Ji MA ; Yun LIU ; Shin KWAK ; Chunlan WU ; Jun WANG ; Baofeng QIN
Chinese Journal of Neurology 2011;44(11):763-767
Objective To quantitatively assess severity of movement disability by analyzing physical activities recorded by an actigraph monitor in patients with neurology disorders.Methods Eighty-one patients with Parkinson' s disease(PD)and 61 patients with acute cerebral infarction(ACI)accompanying impaired upper limb motor function were included in the study.PD patients and ACI patients were treated using the international PD and ACI treatment guidelines,respectively.The patients were asked to wear an Actigraph monitor for 6 days before the treatment in both PD and ACI patient groups and at 24-38 days post-treatment in PD patients or at 28 days post-treatment in ACI patients.The recorded data was analyzed by power-law exponent(PLE)and detrended fluctuation analysis(DFA).Clinically,before and after the treatments,PD patients were evaluated using the conventional Unified Parkinson Disease Rating Scale (UPDRS),and ACI patients were evaluated by assessing upper limb motor function using Fugl-Meyer Assessment(FMA)and Functional Independence Measure(FIM).The correlation of the UPDRS scores with PLE was analyzed in PD patients,and the correlation of FMA or FIM with DFA in ACI patients.Results Both the UPDRS scores and the PLE values in PD patients were improved after the drug administration(UPDRS total:32.8 ± 16.2 and 28.8 ± 14.7,Z =2.080,P =0.038; UPDRS Ⅲ:18.6 ± 8.2 and 15.7±6.8,Z=2.155,P=0.031; PLE:0.98 ±0.25 and 0.82 ±0.21,Z=2.212,P=0.027,before and after the treatment,respectively).There were a linear correlation coefficient of 0.699 between the improvements of total UPDRS scores and the PLE values,and of 0.823 between the UPDRS Ⅲ and the PLE values.FMA,FIM scores and DFA were improved significantly than before treatment(FMA:12.39 ± 8.21 and 30.28 ±7.29,Z=3.016,P =0.004; FIM:8.98 ±7.29 and 13.21 ±7.6,Z =2.282,P=0.038; DFA:0.86 ±0.31 and 0.98 ±0.27,Z =2.360,P =0.036,before and after the treatment,respectively).It also showed linear correlations between the improvements of FMA scores and DFA(r =0.638),and between FIM scores and DFA(r =0.712,both P <0.05).There was no correlation between UPDRS scores and DFA values in PD patients,nor between FIM scores or FMA scores and PLE values in ACI patients.Conclusions Actigraph device can be used to monitor patients activity in movement disorders.Analysis of its PLE can provide a quantitative evaluation in PD while its DFA may provide useful specific assessment of impaired upper limb motor function in ACI patients.It can also be used in quantitatively assessing new drug efficacy.
7.Effect of hypercholesterolemia on the ionic currents in cardiac ventricular myocytes of rats
Yuhong ZHOU ; Ling WANG ; Hongli SHAN ; Yan ZHANG ; Hongli SUN ; Baofeng YANG
Chinese Journal of Pathophysiology 2007;23(5):868-873
AIM: To determine whether chronic hypercholesterolemia affects ionic currents on cardiac ventricular myocytes of rats. METHODS: Whole - cell patch - clamp technique was used to record the ionic currents in single cardiac myocytes isolated from normal cholesterolemia and hypercholesterolemia rats. RESULTS: In the hypercholesterol group (group Ⅱ ), serum total - cholesterol level was significantly higher than that of normal group (group Ⅰ) [ (3. 10 ±tricular myocytes of rats, 50% repolarization of action potential duration (APD50) prolonged from (70. 86 ± 8.12) ms (group Ⅰ) to (116.16±6.90)ms (group Ⅱ) (n=10 in each group, P<0.01); APD90 prolonged from (95.10±7. 27)ms (group Ⅰ ) to (144. 04 ± 7.39)ms (group Ⅱ ) (n = 10 in each group, P < 0. 01 ); at the test potential of - 120 mV, Ik1 increased from ( - 16. 98 ±4. 54) pA/pF(group Ⅰ ) to ( - 19.92 ±4.08) pA/pF (group Ⅱ ) (n = 12 in each group, P < 0. 05 ); at the test potential of 0 mV, ICa- L decreased from ( - 8.56 ± 1.29) pA/pF ( group Ⅰ ) to ( -5. 24 ± 0. 90) pA/pF ( group Ⅱ ) ( n = 10 in each group, P < 0. 01 ); at the test potential of + 60 mV, Ito decreased from (13.20±1.97) pA/pF (group Ⅰ) to (10.30±1.97) pA/pF (group Ⅱ) (n=8 in each group, P<0. 05). CON-CLUSION: Hypercholesterolemia affects the ionic currents on cardiomyocytes of rats greatly, which may be the ionic mechanism of cardiac toxicity induced by hypercholesterolemia.
8.Protective effect of resveratrol on rats with acute myocardial ischemia
Yan ZHANG ; Juan DU ; Wenxiao ZHAO ; Zhenwei PAN ; Baoxin LI ; Baofeng YANG
Chinese Journal of Tissue Engineering Research 2006;10(15):177-179
BACKGROUND: Resveratrol is a naturally occurring phytoalexin present in grapes, peanut and some herbs. It has been demonstrated to produce a variety of biological actions, such as anticancer, antiinflammation. Accumulating line of evidence supported the view that resveratrol may exert protective effect on cardiovascular system. However, its protective mechanism is not completely understood.OBJECTIVE: To investigate the anti-ischemic effect and mechanism of resveratrol (Res) on acute myocardial infarction in rats.DESIGN: Randomly grouping paralleled control study.SETTING: Pharmacological Laboratory of Harbin Medical University, Biopharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory.MATERIALS: The experiment was carried out in Department of Pharmacology of Harbin Medical University from March 2005 to July 2005.Totally 80 male Wistar rats weighting 250-300 g were selected in this study. Among them, 60 rats after operation successful modeling were randomly grouped into 5 groups: sham operation group, blank control group,resveratrol 5 mg/kg, 15 mg/kg and 45 mg/kg groups with 12 in each group.METHODS: Acute myocardial infarction (AMI) model was induced by ligation of the anterior branch of the left coronary artery in rat, Sham operation group: The same suture was put through but not ligated. Resveratrol group: Rats were injected with 5, 15 and 45 resveratrol mg/kg provided by Hunan Huaguang Biological Products Company Limited (batch number: 20050221, purity ≥99%) and ligated after 10 minutes. Model group: The same volume saline was injected for 10 minutes and then rats were ligated. Observe and record ST segment of standard limb lead Ⅱ electrocardiogram (ECG)after 1, 5, 10, 15, 30 minutes after ligating the left anterior decendingcoronary artery. After 6-hour ischemia, the infarct size areas was identified with the myocardium by 2, 3, 5-triphenyltetrazolium chloride (TTC) stain; the activities of serum .creatine kinase (CK)and lactate dehydrogenase (LDH) were determined by spectrophotometric method; the apoptosis in cardiomyocyte was detected by d-UTP end labeling method mediated with tagged deoxynucleotide transferase in situ (TUNEL); apoptosis-related proteins of Bcl-2, Bax and Fas expression were measured with estreptomicina avidin peroxidase chain. Measurement data were compared with t test.MAIN OUTCOME MEATURES: ST increase; the activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH); the infarct size areas and the apoptosis rate in cardiomyocyte; the. expression of apoptosis-related proteins of Bcl-2, Bax and Fas.RESULTS: All of the 60 rats entered the final analysis. ① ST segment raise in high dosage group was lower than that in model group 1, 5 and 10 minutes after ligation (P < 0.05), and it was also lower than that in model 15 and 30 minutes after ligation (P < 0.05). This effect was dose-dependent. ② Infarct size in each dosage group was smaller than that in model group (P < 0.05). This effect was dose-dependent. ③ The activities of CK and LDH in different dosages of resveratrol groups were significantly lower than those in model group (P < 0.05). This effect was dose-dependent. ④ Apoptosis index in model group was higher than different dosages of resveratrol groups (P < 0.05); The expression levels of Bax and Fas proteins in model group were higher than those in high and middle dosages of resveratrol groups (P < 0.05); The expression level of Bcl-2 protein was lower than that in high and middle dosges of resveratrol groups (P < 0.05).These effects were dose-dependent.CONCLUSION: Resveratrol can protect acute myocardial ischemic injury induced by coronary artery of ligated rats, and the effect is dose-dependent.Effect of resveratrol on myocardial ischemia is related to adjusting expressions of Fas, Bcl-2 and Bax and inhibiting myocardial apoptosis.
9.High-cholesterol diet with or without corn oil for establishing atheroscle-rotic model in rabbits
Yi WEN ; Yan ZHOU ; Xiang LIU ; Nanrong ZHANG ; Hongli WANG ; Baofeng LV ; Sanqing JIN
Chinese Journal of Pathophysiology 2014;(6):1148-1152
AIM:To compare the reliability and plaque area between using high-cholesterol diet and high-cho-lesterol diet with corn oil to establish a rabbit atherosclerotic model .METHODS:Eighteen New Zealand rabbits were ran-domly divided into 3 groups (6 rabbits each):normal diet group (group C), high-cholesterol diet group (group H1) and high-cholesterol diet containing 6%corn oil group (group H2).All rabbits were fed for 12 weeks, and their body mea-sured was weighed at the end of every weeks .The serum levels of high-density lipoprotein cholesterol ( HDL-C) , low-den-sity lipoprotein cholesterol ( LDL-C) , total cholesterol ( TC) and triglyceride ( TG) were measured by automatic chemistry analyzer at 0 week and 12 weeks.At the end of 12 weeks, the thoracic aorta of 8-cm length since aortic root was isolated from the rabbit after anesthesia , and stained with Sudan IV or oil red O to verify the existence of plaque .The percentage of plaque area (PA/IA) in the intima area was further calculated by ImageJ 2x software.RESULTS:At the end of 12-week feeding, the serum levels of HDL-C, LDL-C and TC in both group H1 and group H2 were significantly higher than those in group C, and serum TG in group H2 was significantly higher than that in group C .Serum HDL-C in group H2 was signifi-cantly higher than that in group H1, but no significant difference of serum LDL-C, TC and TG between group H1 and group H2 was found .There was no plaque in the intima in group C , and plaques were observed in the intima of all rabbits in group H1 and group H2.Rabbit atherosclerotic models in both group H 1 and group H2 were established with a success rate of 100%.The values of PA/IA in group H1 [(49.74 ±18.78)%] and group H2 [(56.95 ±26.74)%] were both sig-nificantly higher than that in group C (0%), and no significant difference of PA/IA between group H1 and group H2 was observed.CONCLUSION:High-cholesterol diet with or without corn oil can establish a rabbit atherosclerotic model with a success rate of 100%after 12-week feeding , and the percentage of plaque area in the total aortic intimal area is not differ-ent in the 2 feeding methods .
10.Alteration of cardiac M_3 receptor and its relationship with arrhythmias in drug-induced and ischemia-induced arrhythmic models
Yang GAO ; Yan LIU ; Mipeng CIEN ; Danlu LI ; Juan DU ; Yanjie L ; Baofeng YANG
Chinese Journal of Pathophysiology 1989;0(06):-
AIM:To investigate the alteration of cardiac M3 receptor and its relationship with arrhythmias in various arrhythmic models.METHODS:Forty Wistar rats were randomly divided into 4 groups:control,aconitine,BaCl2 and ischemia.In the later three groups,arrhythmias were induced by treatment with aconitine,BaCl2 and coronary artery occlusion,respectively.The arrhythmias were recorded for 1 h.Western blotting was then used to detect M3 receptor contents.RESULTS:Arrhythmias were all induced in each group.In aconitine-induced arrhythmias,duration of arrhythmias and arrhythmia score were significantly increased than those in other two model groups.Western blotting showed that the expression of M3 receptor upregulated 2.3,1.4 and 1.3 folds respectively,more abundant in various arrhythmic groups than that in the normal control.Moreover,M3 receptor expression in aconitine group increased significantly than that in BaCl2 and ischemia group.The arrhythmias and M3 receptor protein expressions in myocytes were positively correlated.CONCLUSION:Arrhythmias upregulate the expression of cardiac M3 receptor.The upregulating levels of M3 receptor proteins diverge strikingly in different arrhythmic models.It is probably that the diversity of increase in M3 receptor is positive related to severity of ventricular arrhythmias.