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Objective:To explore the relationship of NSCL/P with MTHFR gene polymorphism in Xinjiang Uyghur and Han popula-tion and the ethnic difference.Methods:rs1801131 and rs1801133 polymorphism was detected by SNaPshot genotype method in 170 children with NSCL/P and 100 healthy controls of Uyghur and Han population.Results:Rs1801133 TT and T allele was statistically difference between 2 nationalities(P 0.05).Conclusion:Rs1801133 TT and T allele in Han nationality are more likely to suffer from NSCL/P than in Uyghur,rs1801133 CT and CT +TT genotypes are protective factors.Rs1801131AC and rs1801133CC conjoint is relevant to NSCL/P,and the risk in Uyghur is higher than in Han.MTHFR rs1801131 gene polymorphism may not be relat-ed with NSCL/P in Uyghur or Han.
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BACKGROUND: Diabetic cardiomyopathy, a serious complication of diabetes, is an important factor of increased mortality in patients with diabetes. Therefore, providing an effective experimental animal model is particularly important for studying the pathogenesis and treatment methods of diabetic cardiomyopathy. OBJECTIVE:To explore the method of establishing Wistar rat models of diabetic cardiomyopathy. METHODS:Forty rats were randomly divided into the control group (n=10) and diabetic cardiomyopathy group (n=30). The rats in the diabetic cardiomyopathy group were intraperitonealy injected with 60 mg/kg streptozotocin at a time to establish rat models of diabetic cardiomyopathy. The rats in the control group were given the same dosage of citric acid buffer by the same way. The rats in these two groups were al fed with non-fat high-sugar normal diet. RESULTS AND CONCLUSION:Compared with the control group, after 3 weeks of injection with streptozotocinin in rat models of diabetic cardiomyopathy, blood glucose level was significantly increased, myocardial cels arranged in disorder, the nuclei were of different sizes, colagen content in the myocardial tissue was significantly increased, and colagen fibers were thick and disordered. In addition, the mRNA and protein levels of transforming growth factorβ1 and type I colagen, two indices reflecting myocardial fibrosis, were markedly increased. These results indicate that intraperitonealy injecting large doses of streptozotocin (60 mg/kg) at a time and feeding with non-fat high-sugar normal diet could establish a stable rat model of type 1 diabetic cardiomyopathy. This method is safe and effective with high feasibility.
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Objective To evaluate the effect of exogenous hydrogen sulfide (H2 S) on myocardial damage induced by renal ischemia-reperfusion (I/R) in rats.Methods Thirty pathogen-free male Wistar rats,weighing 250-300 g,were randomized into 3 groups (n =10 each) using a random number table:sham operation group (S group); myocardial damage induced by renal I/R group (I/R group); NaHS group.Renal I/R was induced by occlusion of the left kidney for 120 min followed by 60 min reperfusion in anesthetized rats.In NaHS group,NaHS 100 μg/kg was injected intraperitoneally at 20 min before reperfusion.At the end of reperfusion,the rats were sacrificed and the hearts were obtained for determination of malondialdehyde (MDA) content and glutathione peroxidase (GSH-Px) activity in myocardial tissues and for microscopic examination.Results Compared with S group,MDA content was significantly increased,and GSH-Px activity was decreased in I/R and NaHS groups.Compared with I/R group,MDA content was significantly decreased,and GSH-Px activity was increased in NaHS group.The pathological changes of myocardium were significantly attenuated in NaHS group as compared with I/R group.Conclusion Exogenous H2 S can alleviate myocardial damage induced by renal I/R in rats.
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Objective To investigate the effects of physical exercises on cardiac function and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in hypertensive patients combined with diastolic cardiac dysfunction.MethodsA total of 66 essential hypertension patients who had abnormal left ventricular relaxation and normal systolic function were assigned to the intervention group ( n =33 ; doing physical exercises once a day,5 days a week) or control group (n =33 ).All the patients received standard treatment.At 6 months,body weight,blood pressure,heart rate,NT-proBNP,and echocardiography were measured.ResultsAt 6 months,body weight [ (68 ± 7 ) kg vs (72 ± 8 ) kg ],systolic blood pressure [ (135.4 ±5.1) mm Hg (1 mm Hg =0.133 kPa) vs (141.9 ±5.2) mm Hg ],diastolic blood pressure [ (81.1 ±4.0) mm Hg vs (84.7 ±4.6) mm Hg],New York Heart Association class (1.4 ±0.3 vs 1.8 ±0.4),NT-proBNP level [ (526 ± 126 ) ng/L vs (741 ± 189 ) ng/L] were significantly decreased in the intervention group when compared with the control group ( all P ＜ 0.05 ) although left ventricular ejection fraction (LVEF) (62.9 ±6.7 vs 59.0 ±5.6) and E/A ratio ( 1.1 ±0.3 vs 0.9 ±0.3) were significantly increased ( both P ＜ 0.05).ConclusionPhysical exercises could play a role in reduced blood pressure and body weight and improved cardiac function in hypertensive patients with diastolic cardiac dysfunction.
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Objective To identify the genetic variants of WNK4(with no K=lysine kinase)gene in Kazak population in Xinjiang province,to determine whether the WNK4 gene intron 10 polymorphism iS associated with essential hypertension(EH)and to investigate the distribution of genotype and allele frequencies of WNK4 gene. Methods One hundred and ninety-one patients with EH and 173 normal blood pressure controls were included in the study to assess the contribution of polymorphism of WNK4.Direct DNA sequencing was performed to identify the single nucleotide polymorphism(SNP)in 16 SUbjects with EH and 16 subjects of normotension(NT).Then the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method was used for the detection of WNK4 genotype. Results One SNP located in the 10 intron of WNK4 (1156666 base of chromosome 17)was found in the Kazak population.The genotypes of the variants were found to be in Hardy-Weinberg equilibrium.GG,AG,AA genotypes were 88.0%,11.0 oA,1.0%in the EH group and 91.9%,8.1%,0%in the NT group,respectively.The frequencies of genotype and allele in EH group were not significantly different from NT group in Kazak population.Conclusions It suggests that the intron 10 polymorphism of WNK4 gene might be not associated with hypertension in Kazak population.
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Objectives To explore the role of hydrogen sulfide(H_(2)S) in lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats and the underlying mechanisms.Methods Sixty-four Sprague-Dawley rats were randomly divided into four groups: control,LPS(instilled intratracheally to induce ALI),NaHS(H_(2)S donor)+LPS,propargylglycine [inhibitor of cystathionine-?-lyase(CSE),PPG]+LPS.Animals were sacrificed at(4 h) or 8h after agent administration.Lung weight/body weight ratio(LW/BW) was measured and calculated.Morphological changes of lung tissues were observed,H_(2)S concentration and carbon monoxide(CO) level in plasma were tested.Malondialdehyde(MDA) content,CSE activity and heme oxygenase(HO) activity of the lung were determined.Immunohistochemisty technique was performed to examine the expression and the absorbance value of(HO1) protein in lung tissues.Results Compared with control conditions,severe injuries of lung tissues and a raised LW/BW and MDA content were observed in rats treated with LPS.LPS also lead to a drop in plasma H_(2)S concentration and lung CSE activity.The enzyme activity of HO,the protein expression of(HO-1) and plasma CO level increased after LPS instillation. Administration of NaHS before LPS could atten-uated the changes induced by LPS.Pre-administration of PPG exacerbated the injuries induced by LPS,but there was no prominent variation in CO level,HO activity and(HO-1) protein expression compared with those of LPS group.Conclusions Downregulation of H_(2)S/CSE was involved in the pathogenesis of acute lung injury induced by LPS.Exogenous(H_(2)S) provided protection against the lung injuries to some extent,which may be explained by its anti-oxidative effects and the upregulation of CO/(HO-1) system.
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BACKGROUND: Recently, it is investigated that shell of plantain seed is a soluble dietary fiber which can be added into foods to regulate content of cholesterol.OBJECTIVE: To investigate the interventional effect of plantain seed on lipid and its lipid peroxidation in rats with hyperlipidemia.DESIGN: Completely randomized grouping design and controlled animal study.SETTING: Laboratory of Pharmacology and Toxicology for New Drug in Hebei Province.MATERIALS: ① A total of 24 healthy SD rats, of grade I, aged 60-70 days, weighting (210±22) g, of either gender, were selected in this study. ② Basic feed was provided by Experimental Animal Center in Hebei Province,and the fractional mass of each component was mentioned as following:flour 0.25, bran 0.1, corn dust 0.22, bean cake 0.22, fish dust 0.02, bone dust 0.02, grass dust 0.05, salt 0.01, yeast dust 0.02, and sunflower seed 0.03. High fat feed was provided by Experimental Animal Center in Hebei Province, and the fractional mass of each component was mentioned as following: basic 0.9, cholesterol 0.015, lard 0.08, and hyocholic salt 0.003.③ Lipid kit was provided by Baoding Changcheng Clinical Reagent Company, and kits of superoxide dismutase (SOD), catalase (CAT),glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were provided by Nanjing Jiancheng Bioengineering Institute.METHODS: The experiment was completed at the Laboratory of Pharmacology and Toxicology for New Drug in Hebei Province from June to December 2004. ① All 24 rats were randomly divided into 3 groups:normal control group, model group and plantain seed group with 8 in each group. Rats in the normal control group were fed with basic feed. Rats in plantain seed group were fed with high fat feed + 15 g/kg plantain seed and drank routinely. Experimental rats were fed in cages, respectively.Each one was fed with 25 g/d food and drunk freely. The experimental cycle was 12 weeks. ② At the end of experiment, rats were anesthetized to assayed levels of serum triacylglycerol (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), serum SOD and MDA, activities of CAT and SOD in myocardial tissue, content of MDA, and activities of CAT and GSH-Px in hepatic tissue with related kits. ③ Measurement data were compared between each two group with t test.MAIN OUTCOME MEASURES:Comparison of serum lipid level and anti-oxidation among groups at 12 weeks after modeling.RESULTS: All 24 rats were involved in the final analysis. ① At 12 weeks after modeling, activities of SOD in serum and myocardial tissue were lower in model group than those in normal control group and plantain seed group (P ＜ 0.05), but levels of MDA in serum and myocardial tissue were higher in model group than those in normal control group and plantain seed group (P ＜ 0.05). ② At 12weeks after modeling, activities of CAT and GSH-Px in serum and myocardial tissue were lower in model group than those in normal control group and plantain seed group (P ＜ 0.05). ③ At 12 weeks after modeling, levels of TC and TG in serum were higher in model group than those in normal control group and plantain seed group (P ＜ 0.05), but level of HDL-C and ratio between HDL-C and TC in serum were lower in model group than those in normal control group and plantain seed group (P ＜ 0.05).CONCLUSION: Plantain seed at dosage of 15 g/kg can decrease content of lipid and strengthen anti-oxidation of economy in rats with hyperlipidemia.
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BACKGROUND: Great concerns haven been given increasingly on inhibition of nutrient with antioxidation efficacy on lipid peroxidation and its effect on prevention of cardiac vascular disease.OBJECTIVE: To probe into the effects of plantain seed that acts on eliminating oxygenic free radical and antioxidation on lipid metabolism and antioxidation in rats.DESIGN: Randomized control experiment was designed.SETTING: Experimental Room of Pharmacology and Toxicology of New Drug in Hebei Province.PARTICIPANTS: The experiment was performed in Experimental Room of Pharmacology and Toxicology of New Drug in Hebe Province from January to December 2004, in which, 40 SD rats were employed, provided from Hebei Experimental Animal Center, of healthy grade I, mass weighted (210±22) g and of either sex. They were randomized into 5groups, named, blank control, positive control, low dosage experiment group, moderate dosage experiment group and high dosage experiment group, 8 rats in each one.METHODS: In blank control, the rats were bred everyday with basic forage that was tallied with AoAc animal nutrient criteria and they were free of drinking. In positive control, the rats were bred with high-lipid forage and free of drinking. In the groups of low, moderate and high dosages of plantain seed, the rats were bred with 2.5 g/kg, 5 g/kg and 15 g/kg plantain seed successively besides high-lipid forage and they were free of drinking. The weight was measured and the food intake was recorded every week. Fasting blood was collected to check total cholesterol in serum once every two weeks. The experiment was end in 12 weeks. Under anesthesia,the blood was collected from hypogastric aorta to check the level of serum blood lipid and the activities of superoxide dismutase (SOD) and catalase.After blood collection, the heart and liver were extracted immediately for management to measure SOD activity and content of lipid peroxide (LPO)in myocardial tissue and the activities of catalase and glutathione peroxidase in liver tissue.MAIN OUTCOME MEASURES: Level of blood lipid and activities of SOD and catalase in rats.RESULTS: Forty rats were employed and all entered result analysis. [1]Serum total cholesterol: It was lower significantly in high dosage group compared with positive control [(1.40±0.13, 1.83±0.13) mmol/L, P ＜ 0.05].[2] Serum SOD activity: It was lower remarkably in positive control compared with blank control [(174.29±10.33, 193.19±.7813) NU/mg, P ＜ 0.05].[3] LPO content in serum: It was higher significantly in positive control compared with blank control [(3.64±0.26, 2.91±0.50) mmol/mg, P ＜ 0.05]and it was lower significantly in moderate dosage group compared with positive control (3.13±0.26, 3.64±0.26, P ＜ 0.05). [4] Activity of catalase in liver tissue: It was lower remarkably in positive control compared with normal control (34.64±3.26, 44.72±2.67, P ＜ 0.05) and it was higher remarkably in moderate dosage group compared with positive control (44.84±3.79,34.96±3.64, P ＜ 0.05).CONCLUSION: Plantain seed reduces the levels of total cholesterol,triglycerin (TG) and LPO in serum and increases SOD activity. At the concentration of 15 g/kg, plantain seed acts most remarkably on eliminating oxygenic free radical and antioxidation and alleviates lipid metabolic disturbance.
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AIM: To study the regulatory effect of curcumin on expression of heme oxygenase-1 (HO-1) in the lung of rat treated with LPS. METHODS: Eighteen rats were divided into three groups injected with different agents via lingua vein: control group (animals received equivalent saline) , LPS group (animals received a bolus dose of LPS 5 mg?0.5 mL-1?kg-1) and LPS+ curcumin group (animals received AP- 1 inhibitor curcumin 20 mg?0.5 mL-1?kg-120 min before the injection of LPS 5 mg ?0.5 mL-1?kg-1) . The expression of HO-1 mRNA and protein in the lung were examined 7 h after LPS administration by reverse transcribed polymerase chain reaction (RT- PCR) and Western blotting, respectively. Carboxyhemoglobin (HbCO) formation within pulmonary tissue was measured to represent CO content. RESULTS: The results showed that HO- 1 mRNA and protein expression as well as CO content in the lung of rats in LPS group were significantly higher than those in control group (P
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AIM: To study the role of carbon monoxide (CO) in the mechanism of cholecystokinin-octapeptide (CCK-8) for attenuation of acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: Fifty-six adult male rats were randomly divided into seven groups: control group, LPS group, LPS+ZnPP (a specific inhibitor of HO-1) group, LPS+Hemin (Hm, CO donor) group, CCK-8+LPS group, CCK-8+LPS+ZnPP group and CCK-8 group (n=8 for each). Bronchoalveolar lavage was performed 2 h, 6 h and 12 h respectively after treatments. The numbers of polymorphonuclear leukocytes (PMN) in bronchoalveolar lavage fluid (BALF) was detected. The mortality of rats and the structure of lung tissues were observed. MDA and CO contents in lung tissues were also measured. RESULTS: The mortalities of rats were both zero 2 h and 6 h after agent administration. The mortality of rats was higher than control group 12 h after LPS administration. The mortality of rats in LPS+Hm and CCK-8+LPS group were lower than that in LPS group, and its in LPS+ZnPP and CCK-8+LPS+ZnPP group were lower than that in LPS and CCK-8+LPS group, respectively. Lung injury was observed in LPS group. At the same time the number of PMN, MDA and CO content were higher than those in control group. The degree of lung injury, PMN numbers and MDA content were lower, while CO content in LPS+Hm and CCK-8+LPS group were higher than those in LPS group. However, the degree of lung injury, PMN number and MDA content were higher, CO content were lower in LPS+ZnPP and CCK-8+LPS+ZnPP group than those in LPS and CCK-8+LPS group, respectively. CONCLUSION: CCK-8 attenuates the LPS-induced acute lunginjury by means of anti-oxidation and inhibition of PMN aggregation, which are both mediated by CO.
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AIM: To investigate the effect of H_2S on pulmonary artery hypertension during acute lung injury induced by LPS and the interaction between the systems of hydrogen sulfide (H_2S)/cystathionine-?-lyase (CSE) and nitric oxide (NO)/nitric oxide synthase (NOS) in this process. METHODS: Seventy-two adult male rats were randomly divided into four groups: control group, LPS group, LPS+L-NAME group and LPS+propargylglycine (PPG) group. Mean pulmonary artery pressure (mPAP) of each rat was examined at 2 h, 4 h, 6 h and 8 h after treatment. H_2S and NO contents in plasma, NO content, iNOS, cNOS and CSE activity in lung were measured at 4 h or 8 h after treatment, respectively. Expression of iNOS in lung tissue was also detected by immunohistochemistry technique, and the injury of lung was evaluated with morphological changes under microscope. RESULTS: LPS could induce severe lung injury, and mPAP, NO content, iNOS activity and its protein expression in LPS group significantly increased, but cNOS activity, H_2S content and CSE activity decreased compared with those of control group. Administration of L-NAME before LPS could attenuate the changes induced by LPS. Pre-administration of PPG, a CSE inhibitor, exacerbated the injury by LPS, but there was no prominent variation in cNOS activity. CONCLUSION: Reduced endogenous H_2S could increase pulmonary artery hypertension during acute lung injury induced by LPS. There is a negative effect between H_2S/CSE system and NO/NOS system in this process.