1.Protective effect of novel phosphodiesterase 5 inhibitor CPD1 on promoting autophagy activation in hearts of rats with pathological myocardial hypertrophy
Xuedi ZHANG ; Huasui CUI ; Yeding SONG ; Haoyan CHEN ; Xiping CUI ; Fanghong LI ; Yunping MU ; Zijian ZHAO
Chinese Journal of Comparative Medicine 2025;35(8):29-38
Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180~200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P<0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P<0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.
2.Protective effect of novel phosphodiesterase 5 inhibitor CPD1 on promoting autophagy activation in hearts of rats with pathological myocardial hypertrophy
Xuedi ZHANG ; Huasui CUI ; Yeding SONG ; Haoyan CHEN ; Xiping CUI ; Fanghong LI ; Yunping MU ; Zijian ZHAO
Chinese Journal of Comparative Medicine 2025;35(8):29-38
Objective To investigate the therapeutic effects of the newly developed phosphodiesterase 5 inhibitor,CPD1,on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,and its impact on activation of the autophagy signaling pathway in myocardial tissue.Methods Male Sprague Dawley rats weighing 180~200 g were divided randomly into five groups:Control,Sham,model(AAC),CPD1 treatment(AAC-CPD1,5 mg/kg),and sildenafil treatment(AAC-Sif,20 mg/kg)groups.Rats in all groups except the Control group underwent blunt dissection of the abdominal aorta at the branch point of the left renal artery.Rats in the AAC and treatment groups also underwent constriction and ligation surgery,while rats in the Sham group underwent dissection without ligation.After 3 days of modeling,rats in the treatment groups received either CPD1 or sildenafil via gavage,while rats in the Control,Sham,and AAC groups received an equal volume of physiological saline by gavage,once daily for 8 weeks.Small-animal ultra-high-resolution echocardiography and left ventricular catheterization were employed to assess left heart function and the heart mass index,and expression levels of the hypertrophy indicator,atrial natriuretic peptide(ANP),the key autophagy pathway factor,p62,and LC3A/B in rat left heart tissue were evaluated by Western blot and reverse transcription-polymerase chain reaction.Results Abdominal aortic stenosis affected left heart function in rats,characterized by an increased cardiac mass index and significant enlargement of myocardial cell cross-sectional area.ANP expression levels in left heart tissue were significantly elevated(P<0.05),while autophagy signaling activity was reduced,with notable accumulation of LC3Ⅰprotein and reduced conversion to LC3Ⅱ.Expression levels of p62 protein were significantly increased.CPD1 and sildenafil significantly improved left ventricular function in AAC rats,reduced cardiac hypertrophy,inhibited expression levels of ANP and p62 proteins(P<0.05),activated autophagy signaling,and promoted the conversion of LC3Ⅰ to LC3Ⅱ.Notably,low-dose CPD1 treatment was equivalent to high-dose sildenafil.Conclusions CPD1 promotes the activation of the autophagy signaling pathway in left heart tissue,inhibits the expression of p62 and ANP,reduces the cross-sectional area of myocardial cells,and improves pathological myocardial hypertrophy and left heart function impairment caused by AAC.CPD1 also has the advantage of a lower effective dose compared with sildenafil,offering a new treatment option for pathological myocardial hypertrophy.
3.The correlation between frailty and cardiac autonomic nervous function in elderly patients
Xuezhai ZENG ; Yaodan LIANG ; Jing SHI ; Yu GAN ; Ning SUN ; Di GUO ; Lingling CUI ; Jihong ZHOU ; Xuedi LI ; Na JIA ; Hua WANG ; Deping LIU ; Jiefu YANG
Chinese Journal of Geriatrics 2021;40(6):716-721
Objective:To assess the correlation between frailty and cardiac autonomic nervous system function in elderly patients.Methods:Elderly hospitalized patients aged 65 years and over were enrolled and assessed for frailty by using the clinical frailty scale.Cardiac autonomic modulation was evaluated by heart rate variability analysis through 24 h electrocardiogram recording.Results:A total of 180 elderly patients were enrolled in this study, including 66 patients with frailty and 114 patients without frailty.The mean age of the frailty group was higher than that of the non-frailty group(79.8±6.0 vs.75.0±6.3, t=5.030, P<0.001). The proportions of patients with hypertension, stroke/transient cerebral ischemia attack(TIA), heart failure and osteoarthritis were higher in the frailty group than in the non-frailty group(all P<0.05). Compared with the non-frailty group, the standard deviation of normal-to-normal intervals(SDNN)[103.0(76.0, 121.2) vs.107.5(92.0, 136.0), Z=-2.108, P=0.035], the standard deviation of the averages of NN intervals in all 5-min segments(SDANN)[86.0(67.7, 106.5) vs.97.5(78.0, 126.0), Z=-2.694, P=0.007], normalized low frequency(LFnorm)(53.1±13.0 vs.59.3±13.9, t=-3.024, P=0.003)and low frequency/high frequency(LF/HF)ratio[1.2(1.0, 1.4) vs.1.4(1.1, 1.7), Z=-3.041, P=0.002]were decreased and normalized high frequency(HFnorm)(36.8±9.2 vs.32.2±10.7, t=3.033, P=0.003)was increased in the frailty group.HFnorm in the frailty group was significantly higher than that in the non-frailty group.The incidents of SDANN<92 ms, LFnorm<50 nU, HFnorm>32 nU and LF/HF ratio<1.5 were higher in the frailty group than in the non-frailty group(59.1% or 39/66 vs.41.2% or 47/114, 42.4% or 28/66 vs.22.8% or 26/114, 72.7% or 48/66 vs.49.1% or 56/114, 84.8% or 56/66 vs.65.8% or 75/114, χ2=5.346, 7.660, 9.547, 7.664, P=0.021, 0.006, 0.002, 0.006). Logistic multivariate regression analysis showed that LFnorm, HFnorm and LF/HF ratio were correlated with frailty( OR=0.971, 1.039 and 0.333, all P<0.05), and HFnorm>32 nU and LF/HF ratio<1.5 were risk factors for frailty( OR=2.401 and 2.773, both P<0.05). Conclusions:Cardiac autonomic nerve system function is impaired in elderly frail patients, with the imbalance between the sympathetic and vagus nerves.Therefore particular attention should be paid to heart rate variability in elderly patients with frailty.
4.Cardiac autonomic nerve function in elderly patients with frailty
Xuezhai ZENG ; Yaodan LIANG ; Jing SHI ; Yu GAN ; Ning SUN ; Di GUO ; Lingling CUI ; Jihong ZHOU ; Xuedi LI ; Na JIA ; Hua WANG ; Deping LIU ; Jiefu YANG
Chinese Journal of General Practitioners 2020;19(10):908-912
Objective:To assess the cardiac autonomic nervous function in elderly patients with frailty.Methods:Patients aged ≥ 65 years old admitted in Beijing Hospital from September 2018 to August 2019 were enrolled in this study. Clinical frailty score was used to assess the frailty. The cardiac autonomic modulation was evaluated by sinus heart rate turbulence analysis through 24 h electrocardiogram recording.Results:A total of 129 elderly patients were finally enrolled in this study with a mean age of (77.5±6.4) years, 58.1% of them were male. There were 53 patients in frail group and 76 patients in non-frail group. The age of the frailty group was significantly higher than that of the non-frailty group [(80.5±5.5) vs.(75.3±6.2)]; the prevalence of hypertension [84.9%(45/53)], heart failure [32.1%(17/53)] and peripheral vascular diseases [32.1%(17/53)] in the frailty group was significantly higher than that in the non-frailty group [65.8%(50/76), 1.3%(1/76), 17.1%(13/76); t=5.001, χ 2=5.879, 24.606, 3.921; all P<0.05]. Compared with non-frailty group, turbulence onset (TO) [-0.05(-0.92, 0.82)% vs. -0.74(-1.58, 0)%; Z=2.616, P=0.009] was significantly higher in frailty group, while turbulence slope (TS) [2.34(1.30, 5.00)ms/RR vs. 4.34(2.66, 6.39)ms/RR; Z=-3.048, P=0.002] was significantly lower. The rate of TO abnormality [49.1% (26/53) vs. 26.3%(20/76), χ 2=7.038, P=0.008] and TS abnormality [34.7%(29/53) vs. 21.0%(16/76); χ 2=15.579, P<0.001] in the frailty group was significantly higher than that in the non-frailty group. Multivariate logistic regression analysis showed that TO abnormality( OR=2.970, P=0.010, 95 %CI:1.300-6.785) and TS abnormality( OR=3.618, P=0.003, 95 %CI:1.565-8.364) were correlated with frailty. Conclusion:Cardiac autonomic nerve function may be impaired in elderly frail patients, and decreased vagal nerve tension may be presented.
5.Detection of serum specific IgE to crab allergen in different group people with extracted Eriocheir sinensis allergens
Haibo HUANG ; Weiwei CHEN ; Wei CHEN ; Juan LI ; Xuedi LI ; Qunying LIU
Chinese Journal of Biochemical Pharmaceutics 2010;31(2):128-130
Purpose To detect serum specific IgE to crab allergen in different group people with extracted Eriocheir sinensis allergic proteins and to provide laboratorial evaluation for diagnosis and treatment of crab anaphylaxis.Methods Micro titer plates were coated with the allergic proteins extracted from crab.A total of 1907 serum samples from 3 group people were detected for specific IgE to crab allergens with indirect ELISA.The serological IgE level of different group people allergic to crab food wag compared and analyzed.Results 203 individuals were serum specific IgE positive in the detected 1 907 serum samples,and the positire rates Wag 10.65 percent(203/1 907).The statistical analysis showed that the difference of serum IgE positire rates among the 3 group people wag very significant(P<0.01).Conclusion The detection of serum specific IgE using allergic proteins extracted from crab has diagnostic meaning,since it can be used as laboratorial evaluation for clinical diagnosis and treatment of crab anaphylaxis.

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