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1.
China Pharmacy ; (12): 1246-1251, 2021.
Article in Chinese | WPRIM | ID: wpr-876894

ABSTRACT

OBJECTIVE:To st udy the effects of α7 nicotinic acetylcholine receptor agonists (PNU282987)on improving cardiac remodeling of mice and Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway. METHODS:Male Kunming mice were randomly divided into normal control group ,model group ,propranolol group (positive control,i.g. 40 mg/kg)and PNU 282987 low-dose,medium-close and high-dose groups (intraperitoneal injection of 0.5,1.0,3.0 mg/kg),with 10 mice in each group. Except for the normal control group ,mice in the other groups were given isoproterenol (ISO,30 mg/kg) subcutaneously for 7 days to induce the cardiac remodeling model. After 30 minutes of ISO injection , administration groups were given relevant liquid ,once a day ,for 7 consecutive days. Twelve hours after last administration ,the left ventricular ejection fraction (EF)and left ventricular short axis shortening rate (FS)of mice in each group were measured ,and the whole heart mass index (HMI)was calculated ;the pathological changes of myocardium were observed. The serum contents of lactate dehydrogenase (LDH),creatine kinase (CK),tumor necrosis factor α(TNF-α),interleukin 6(IL-6),the protein expression of intercellular adhesion molecule 1(ICAM-1)and adhesion molecule 1(VCAM-1)were also determined. The ratios of p-JAK2/JAK2,p-STAT3/STAT3 in myocardial tissue were detected. RESULTS :Compared with normal control group ,EF and FS of model group were significantly reduced ,HMI,the contents of LDH,CK,TNF-α and IL-6,the protein expression of ICAM- 1 and VCAM- 1,the ratio of p-JAK 2/JAK2 and p-STAT 3/STAT3 were increased significantly (P<0.05 or P<0.01); blue collagen deposition in the interstitium of myocardium was obvious,and the degree of fibrosis was severe. Compared with model group , the EF and FS of the mice in the medium-dose and high-dose groups were increased significantly , HMI (except for PNU 282987 medium-dose group ),the contents of LDH (except for PNU 282987 medium-dose group ),CK,TNF-α and IL-6,the protein expression of ICAM- 1 and VCAM- 1,the ratio of p-JAK 2/JAK2 and p-STAT 3/STAT3 were decreased significantly (P<0.05 or P< 0.01);blue collagen deposition in the myocardial interstitium was significantly reduced ,and the degree of myocardial fibrosis was significantly reduced. There was no significant difference in the comparison of the above indicators in PNU 282987 low-dose group (P>0.05). CONCLUSIONS :PNU282987 can improve cardiac remodeling of mice ,the mechanism of which may be associated with inhibiting JAK 2/STAT3 signaling pathway.

2.
Chinese Journal of Pediatrics ; (12): 101-106, 2020.
Article in Chinese | WPRIM | ID: wpr-799308

ABSTRACT

Objective@#To analyze the genetic characteristics of a five generations pedigree with homozygous familial hypercholesterolemia (HoFH).@*Methods@#Prospective study. Twenty family members included a proband diagnosed as familial hyperlipidemia at the cardiology Department of Xi′an Children′s Hospital in October 2018 were research object. Clinical data were collected. Genome DNAs were extracted. Whole exons sequencing was performed on the proband using target capture next generation sequencing. Candidate gene mutation sites identified by bioinformatics were verified by Sanger sequencing in the family members. The genotype-phenotype correlation of the pedigree was analyzed between heterozygous mutation carriers and non-carriers.@*Results@#The proband was a 7-years and 10-month-old boy. He was born with a roundgreen bean size yellow skin protuberance in the skin of the coccyx. Since the age of 3-4 years old, xanthoma-like lesions with a diameter of 0.5-1.5 cm gradually appeared in the skin of bilateral elbow joints, knee joints and Achilles tendon. The height, weight and intellectual development of the child were the same as those of normal children at the same age. No similar xanthoma-like lesion was found in the other family members. The proband′s total cholesterol (TC) reached 18.16-21.24 mmol/L, and his low density lipoproteincholesterol (LDL-C) was 14.08-15.51 mmol/L. Carotid ultrasonography showed diffuse sclerotic plaques in bilateral carotid and vertebral arteries, and color Doppler echocardiography revealed aortic valve thickening and calcification. Gene testing identified that the proband carried a homozygous mutation C. 418G>A (p. E140K) in LDLR gene inherited from his parents who had a consanguineous marriage and carried a heterozygous mutation of LDLR-E140K, respectively.The TC, LDL-C and apolipoproteinB (ApoB) of LDLR-E140K gene heterozygous carriers ((8.40±0.13), (6.79±0.01) and (1.95±0.05) mmol/L, respectively) were significantly higher than those of non-carriers ((4.59±0.28), (3.35±0.39) and (0.86±0.10) mmol/L, t=7.269, 4.595, 6.311, respectively, P<0.05).@*Conclusions@#LDLR-E140K gene homozygous mutation is first reported to be associated with most severe phenotype HoFH. The genotype-phenotype analysis of the pedigree shows that the clinical phenotype of the proband with homozygous mutation is the most serious, and all the heterozygous mutation carriers present with hypercholesterolemia phenotype. The investigation confirms that LDLR-E140K is the pathogenic variation of familial hyperlipidemia.

3.
China Modern Doctor ; (36): 34-36, 2018.
Article in Chinese | WPRIM | ID: wpr-1037936

ABSTRACT

Objective To study the existence and significance of cholesterol-intestinal hepatic circulation in rabbits by establishing a model of enterohepatic circulation and blocking enterohepatic circulation. Methods In this experiment, the experimental group and the control group were set up to conduct high-cholesterol diets and ordinary diets for differential feeding. By establishing a model of enterohepatic circulation and blocking enterohepatic circulation, cholesterol oxidase method was used to measure serum cholesterol concentration in the experimental group and the control group respectively. Based on the statistical analysis of the data for 6 months, the phenomenon of enterohepatic circulation of cholesterol was studied. Results Based on the data of 6 months, the serum cholesterol concentrations of rabbits in groups Aand Cwere gradually increased. After two months, the hypercholesterolemia was significant in the rabbits in group C. The increase degree of serum cholesterol concentration in the rabbits in group Awas weaker than that in group C. Hypercholesterolemia had no obvious effect. There was statistically significant difference between group Aand group C (P<0. 05); serum cholesterol concentration in rabbits in group Dwas increased slightly, but the increase was not significant. The increase of serum cholesterol concentration in group Bwas more significant than that of group D. There was a statistically significant difference between group Band group D (P<0. 05). The serum TC-time line graph was plotted with the serum cholesterol concentration in each group as the ordinate and the time as the abscissa. Compared with group A, the serum cholesterol was increased significantly in group C. Compared with group D, the serum cholesterol in group Bwas increased significantly. Conclusion This experiment shows that the cholesterol enterohepatic circulation phenomenon exists in rabbits. By blocking the enterohepatic circulation in rabbits, it has a certain effect on lowering the content of serum cholesterol in rabbits. This will provide a theoretical basis for further studying the role of blocking enterohepatic circulation in reducing cholesterol levels in the body. It provides new ideas for the clinical treatment of hypercholesterolemia by blocking the cholesterol enterohepatic circulation in clinical practice and points a direction for drug development.

4.
Article in Chinese | WPRIM | ID: wpr-344178

ABSTRACT

Essential tremor (ET) is one of the most common movement disorders. Its clinical manifestations not only include typical kinetic and/or postural tremors, but also other non-motor symptoms such as cognitive dysfunction, sleep disturbance, and dysosmia. The exact etiology and pathogenesis of ET is still unknown. Approximately 60% of ET patients have a family history, and genetic factor plays an important role in the onset of the disease. Researchers have so far identified 3 genetic loci (ETM 1-3) through family studies, and proposed additional causative genes such as FUS, HTRA2, TENM4, NOS3 and susceptibility genes such as LINGO, SLC1A2, and GABA. This review focuses on the progress made in genetic research on ET.


Subject(s)
Humans , Essential Tremor , Genetics , Genetic Predisposition to Disease , Genetic Research , High-Temperature Requirement A Serine Peptidase 2 , Genetics , Membrane Proteins , Genetics , Nerve Tissue Proteins , Genetics , RNA-Binding Protein FUS , Genetics
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