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Objective To investigate the correlation between ABCB1 gene C3435T polymorphism and clinical efficacy of metoprolol,provided a theoretical basis for the precise treatment of hypertension. Methods A total of 120 patients with essential hypertension level 1 or level 2 and a resting heart rate of 80 beats were enrolled in the hospital from October 2016 to October 2017 at the First Affiliated Hospital of Jiamusi University.According to ABCB1 C3435T genotype,all patients were divided into CC group(n=40),CT group(n=57),TT group(n=16)and given oral metoprolol sustained-release tablets 47.5 mg/d.The metoprolol plasma concentration were mea-sured after one week.All subjects followed up to record the mean blood pressure and mean heart rate before and after treatment after four weeks,were compared the changes in blood pressure and heart rate before and after treatment and analyzed the clinical efficacy.Results The standard plasma concentration in group TT[(39.23±6.42)μg/L vs. (45.68±7.43)μg/L],the difference of mean systolic blood pressure before and after treatment in TT group[(18.8± 11.13)mmHg vs.(44±9.05)mmHg],the difference of mean systolic blood pressure before and after treatment in CT group[(26.91±9.33)mmHg vs.(44±9.05)mmHg],the difference of mean diastolic blood pressure before and after treatment in TT group[(11.6 ± 6.59)mmHg vs.(23.75 ± 7.47)mmHg],the difference of mean diastolic blood pressure before and after treatment in CT group[(14.73 ± 6.02)mmHg vs.(23.75 ± 7.47)mmHg]were significantly lower than those in CC group(all P<0.01).After treatment,the antihypertensive effect of CC group was significantly better than TT group(χ2= 6.132,P = 0.013). There was no significant difference in the rate of heart rate among three groups(χ2= 0.484,P = 0.785). There was no significant difference in the mean heart rate among the three groups before and after treatment(F = 1.278,P = 0.293). Conclusions The differences among three groups of genotype patients showed that the different genotypes of ABCB1 gene C3435T were related to the clinical efficacy of metoprolol,which provide a new idea and theoretical basis for the precise treatment of hypertension.
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Objective To explore the expressions of endoplasmic reticulum stress (ERs) related factors including inositol requiring enzyme-1α(IRE1αα),p-IRE1 α,c-jun N-terminal Kinase(JNK),and p-JNK in rats with non-alcoholic fatty liver disease,and to investigate the effect of intervention with glucagon-like peptide 1 (GLP-1) analogue.Methods Forty male Sprague-Dawley rats were divided into normal chow group(n =15) and high-fat diet group(n=25).After 12 weeks,5 rats of each group were used to assess the establishment of rat models with non-alcoholic fatty liver disease.Then the high-fat diet group rats were divided into high-fat diet group (HF,n =10) and GLP-1 group(HG,n=10) and treated with normal saline and GLP-1 analogue for4 weeks respectively.Body weight and biochemical markers in rats were measured.The expressions of IRE1α,p-IRE1α,JNK,and p-JNK were measured by Western blot.Results Compared with the NC group,the levels of body weight,plasma triglyceride (TG),total cholesterol (TC),low density lipoprotein-cholesterol (LDL-C),alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in HF group were significantly higher (all P ＜ 0.01),high density lipoprotein-cholesterol(HDL-C) was decreased(P＜0.01),and p-IRE1 α/IRE1 α and p-JNK/JNK were increased(P＜0.05 and P＜0.01).After GLP-1 treatment,body weight,plasma TG,TC,LDL-C,AST,ALT in HF group were significantly lowered(P＜0.05 or P＜0.01),HDL-C was increased(P＜0.01),p-IRE1 α/IRE1 α and p-JNK/JNK were decreased (P＜0.05 and P＜0.01).Conclusion GLP-1 analogue may improve hepatic steatosis via regulating ERs related IRE1 α-JNK signaling pathway.
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<p><b>OBJECTIVE</b>To investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress injury using a rat model of non-alcoholic fatty liver disease.</p><p><b>METHODS</b>Sixty male Sprague-Dawley rats were fed 12 weeks of either a diet of normal chow (NC), for use as controls (n =15) or high-fat chow (HF), for use as models (n =45).The NC rats were administered normal saline, while the HF rats were treated with either normal saline (NS), for use as untreated model controls (n =10), low-dose GLP-1 (LG, 50 mutg/kg; n =10), mid-dose GLP-1 (MG, 100 mutg/kg; n =10), or high-dose GLP-1 (HG, 200 mug/kg; n =10); all treatments lasted for 4 weeks.The rats' weight, levels of serum biochemical markers (triglycerides, total cholesterol, high-density lipoproteincholesterol, low-density lipoprotein-cholesterol, alanine arninotransferase, and aspartate aminotransferase), levels of superoxide dismutase (SOD) and malondialdehyde (MDA), and expression of CYP2E1 mRNA and protein in liver homogenates were measured.The F test, t-test, least significant difference test and Dunnett's T3 test were used for statistical analyses.</p><p><b>RESULTS</b>Compared with the NC group, the rars in the NS group showed significantly lower SOD (165.81 ± 11.64 vs.192.89 ± 16.53 U/mg, P < 0.05), significantly higher MDA (7.30 ± 1.79 vs.3.10 ± 1.30 nmol/ mg, P < 0.05), and significantly higher expressions of CYP2E1 mRNA and protein (both P < 0.05).After GLP1 treatment, the rats in the LG, MG and HG groups showed increased levels of SOD (compared to the NS group; 171.44 ± 9.80 vs.177.66 ± 14.77 vs.186.17 ± 15.43 U/mg; only the HG group had P < 0.05), significantly decreased levels of MDA (compared to the NS group; 5.16 ± 1.45 vs.4.08 ± 1.22 vs.3.31 ± 1.14 nmol/mg; all P < 0.05], and decreased levels of CYP2E1 mRNA and protein expressions (CYP2E1 mRNA:only the HG group had P < 0.05; CYP2E1 protein: both the MG and HG groups had P < 0.05).</p><p><b>CONCLUSION</b>GLP-1 treatment can improve oxidative stress injury, suggesting its potential as a therapeutic agent for non-alcoholic fatty liver disease.</p>
Subject(s)
Animals , Male , Rats , Aspartate Aminotransferases , Cytochrome P-450 CYP2E1 , Glucagon-Like Peptide 1 , Metabolism , Malondialdehyde , Non-alcoholic Fatty Liver Disease , Metabolism , Oxidative Stress , Rats, Sprague-Dawley , Superoxide Dismutase , TriglyceridesABSTRACT
AIM: To investigate the influence of exogenous somatostatin (stilamin) on pancreatic blood flow in normal rats or rats with acute necrotizing pancreatitis (ANP).METHODS: Pancreatic blood flow (PBF) was detected with computerized tissue blood flowmeter and rats with ANP were triggered with sodium taurocholate. Metabolites of eicosanoids in plasma were determined with radioimmunoassay. Other laboratory tests including histopathologic observation under optical or electron microscope were used. RESULTS: There was a significant decrease in PBF in normal rats after stilamin administration in comparison with that before use of the drug. There was significant decrease in PBF after onset of ANP, but, compared with that in ANP group, significant increase was shown in SS(stilamin)+ANP group. Plasma thromboxin-B 2(TXB 2) in ANP group at 6 hours after ANP was significantly higher, with increase of 4.5 times, than that in Sham(sham operated) group while TXB 2, detected each time during the course of ANP, significantly decreased in SS+ANP group. 6-Keto-prostagland in F 1? (6-Keto-PGF 1? ) at 6 h after ANP was significantly higher, and the ratio of TXB 2/6-Keto-PGF 1? , significantly lower in SS+ANP group than that in ANP group. Lessened necrosis of acinar cells, along with much fewer microthrombi in microvessels in SS+ANP group, was shown by pathologic scoring or electron microscope than that in ANP group.CONCLUSION: Administration of exogenous somatostatin leads to the decrease in PBF in physiological setting but it attenuates pancreatic ischemia in SS+ANP group, which may be attributed to correction of abnormal metabolism of eicosanoids, improvement of pancreatic microcirculation and cytoprotection of acinar cells as well.
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The effects of tetramethylpy-razine (TMP) on pancreatic blood flow and survival rate were studied in sodium tarocholate-in-duced acute pancreatitis (AP) in rats. The results showed that pancreatic relative blood flow and pancreatic tissue perfusion were significantly increased and the pathologic changes and survival rate were improved in TMP treated group-s. Plasma value of TXB2?6-Keto-PGF1? and platelet aggregation rate (PAR) were also mea-sured. We found that TMP could maintain the balance between TXA2 and PGI2 and lower the elevated PAR. It was suggested that TMP has therapeutic effect on AP in rats through improving pancreatic microcirculation; which was related to the maintanance of the balance between PGI2 and TXA2.