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Study On The Effect Of Smoking On Glycolipids Metabolism And The Intervention Effect Of Andrographolide

Posted on:2020-12-29Degree:MasterType:Thesis
Country:ChinaCandidate:A H HanFull Text:PDF
GTID:2404330626950550Subject:Public health
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Abnormal glucose and lipid metabolism is a state of abnormal blood sugar and blood lipid secretion,the main feature is the metabolic syndrome.There are many reasons for the abnormal metabolism of glycolipids,which are not fully elucidated.The metabolic syndrome caused by it can significantly increase the risk of cardiovascular events.For example,the retrospective analysis results from USA indicated that metabolic synthesis increased the risk of myocardial infarction by 1.01 times,the risk of stroke increased by 1.26 times,and the risk of myocardial infarction combined with stroke increased by 1.05 times.In China,971 patients with metabolic syndrome(aged ≥40 years)were followed up for 5 years,and the cardiovascular events incidence rate was 5.5 times higher than that of the control group.Smoking is considered to be closely related to the development of various diseases such as cancer,cardiovascular disease and respiratory injury.The smoking epidemiology survey conducted in 1996 and 2002 showed that the current smoking rate in China is 35.3% and 31.4%,respectively.The number of smokers in China is estimated to be 350 million according to the smoking rate and the 2000 census results;The results in this two surveys of passive smoking rate among non-smokers were nearly equal,at 53% and 51.9%,respectively.At present,smoking problems in China are becoming more and more serious.Study on the relationships between smoking and glycolipid metabolism have been attracted the attention of different scholars,however the specific prevention methods and related drug recommendations are not clear.Andrographis paniculata is a kind of genus,and its purified products,andrographolide,is widely used in the intervention of inflammation and other immune reactions caused by smoking.The population cohort of adult chronic diseases and risk factors monitoring in Jiangsu Province will be used as the basis of the data in this paper.The male population is used as the research object to investigate the relationship between smoking and glycolipid metabolism.Meanwhile,the animal model of diabetic mice was constructed to investigate the effect of andrographolide on blood glucose and blood lipids in diabetic mice exposed to smoke.The objective of this study is to provide theoretical guidance for tobacco control and the prevention and control of diabetes.PartⅠ Epidemiological study on the relationship between smoking and glycolipid metabolismObjective: To explore the relationship between smoking and glycolipid metabolismMethods: A multi-stage cluster sampling method was used to select 3038 adult males from Jiangsu Province as the survey subjects.ANOVA was used to analyze the differences between the smoking and glucose and lipid metabolism related indicators.Chi-square test was used to explore the relationship between smoking and hyperglycemia and dyslipidemia.Confounding factors were adjusted in unconditional multivariate Logistic regression analysis to analyze the relationship between smoking and glucose and lipid metabolism disorders in male population.Results: The fasting blood glucose in severe smokers with ≥30 package years was significantly higher than that in non-smokers(6.05 ± 1.77 mmol/L vs 5.89 ± 1.56 mmol/L,P<0.05),and the number of smoking packs in patients with hyperglycemia(16.07,95% CI: 14.80-17.35)was more than that in non-hyperglycemia(14.06,95% CI: 13.18-14.94,P<0.05).The level of TG in smokers with 0 to 20 cigarettes/day was the highest(1.71 ± 1.73 mmol/L,P<0.05)among the groups;compared with non-smokers(level of TG was 1.58 ± 1.49 mmol/L),smokers in the 0 to 15 package year(1.72 ± 1.64 mmol/L)and 15 to 30 package years(1.86 ± 1.96 mmol/L)increased significantly(P<0.05);the levels of HDL-C in 0-15 and ≥30 package year of smokers were significantly different than that of non-smokers(P<0.05).Unconditional multivariate Logistic regression analysis showed that age,BMI,and systolic blood pressure were the important risk factors for glycolipid metabolism disorder.After adjusting for confounding factors,there was a dose-response relationship between smoking count and smoking package years and hyperglycemia;the OR value increased with the increase of smoking.Among the investigators,especially in the aged <55 years and BMI≥25kg /m2,the moderate smokers with 15 to 30 package years and the heavy smokers with a number of≥30 package years were positively correlated with dyslipidemia,the OR values were 1.433(95%CI:1.071-1.917,P<0.05),1.505(95% CI: 1.071-2.115,P<0.05)and 1.441(95% CI: 1.055-1.969,P < 0.05)respectively.Conclusion: Smoking has a certain effect on glucose and lipid metabolism in male smokers.The amounts of smoking in the patients with dyslipidemia and hyperglycemia were higher than that of non-dyslipidemia and non-hyperglycemia subjects.After stratified analysis,smoking will increase dyslipidemia and hyperglycemia risk and there is a dose-effect relationship.PartⅡ Effects of andrographolide on blood glucose and lipids in diabetic mice exposed to smokeObjective: To investigate the effects of andrographolide on blood glucose and lipid metabolism,and serum inflammatory factors in diabetic mice exposed to cigarette smoke;and to understand partial molecular mechanism of andrographolide on smoking and diabetes;to provide evidences for the control of smoking and diabetes.Methods: 120 SPF grade C57BL/6J strain mice were divided into six groups,20 in each group,using the random number table method.G1 was the normal control group,G2 was the simple high glucose group,G3 was the simple smoke exposure group;G4 was the smoke exposure + high glucose group,G5 smoke exposure + andrographolide group;G6 smoke exposure + high glucose + andrographolide group.G2,G4,and G6 groups were fed with high-fat and high-sugar diet for one month,then STZ was injected intraperitoneally for 2 to 4 days.The control group maintained clean grade feed and injected the same amount of citrate buffer.After one week,3 mices were selected from G2,G4 and G6 group randomly used to measure fasting blood glucose(FBG)by collecting the venous blood of the eye,and the mice diabetic model was successful with fasting blood glucose greater than 11.1 mmol/L.The G3,G4,G5,and G6 groups were exposed to 20 cigarettes of smoke every day between 9:00 and 10:00 for 3 months.The body weight,blood glucose-related index,blood lipids,liver glycogen content and serum inflammatory factor levels of each group were tested at the end of the experiment.Results: This experiment successfully established a mice model of diabetes.There were significant differences in body weight,blood glucose,blood lipids,hepatic glycogen and serum inflammatory factors among the experimental groups.The body weight in G2 group showed a significant decrease compared with the G1 group(P<0.05);compared with the G3 group,body weights in G4,G5 and G6 were significantly different(P<0.05).The results of glucose tolerance test indicated that the level of FPG in G2(9.45 ± 1.26 mmol/L)and G4(10.02 ± 0.39 mmol/L)were significantly increased compared with G1(7.00 ± 0.95 mmol/L)group.The initial blood glucose level was lower in the G6 group than that in the G4 group (8.16 ± 1.44 VS 10.02 ± 0.39 mmol/L,P<0.05),and the peak blood glucose level at 15 minutes was lower than that in G4 group(19.43 ± 1.60 VS 24.23 ± 0.88 mmol/L,P<0.05).The results of insulin tolerance test showed that the initial blood glucose in G4 group(11.00 ± 0.90 mmol/L)was significantly higher than that in G1 group(7.49 ± 0.60 mmol/L)(P<0.05).At the same time,it was found that the hypoglycemic effect of insulin in G4 group was not obvious at 15 min,30min and 60 min,and the level of blood glucose at these time period was higher than that in G1 group(P<0.05).The initial blood glucose level was lower in G6 group than that in G4 group(8.83 ± 0.76 VS 11.00 ± 0.90 mmol/L,P<0.05).The blood glucose levels of,15 min,30min and 60 min in G6 group were also significant lower than those in G4 group(P<0.05).The fasting blood glucose levels in G2(10.11 ± 1.94mmol/L),G3(9.58 ± 0.56 mmol/L)and G4(11.02 ± 0.90 mmol/l)groups were significantly higher than those in G1 group(6.99 ± 0.80mmol/L)(P<0.05),meanwhile it was lower in G5 group(8.20 ± 0.67 mmol/L)than that in G3 group,G6 group(8.82 ± 0.76 mmol/L)was lower than that in G4 group.Compared with G1 group,the level of total cholesterol and triglyceride in G4 group were significantly decreased(P<0.05);TNF-α and IL-6 secretion levels in G2 group and G3 group were significantly higher than that in G1 group,G5 group was lower than that in G3 group,and G6 group was lower than that in G4 group(P<0.05).The results of PAS glycogen staining showed that the G2,G3 and G4 groups had lower PAS glycogen content in the liver tissue of the mice than that in G1 group,especilly in G4 group,indicating that the liver glycogen decreased significantly;compared with the G3 group,the G5 group was darker in color and the cells were arranged neatly,indicating that the level of glycogen in G5 was elevated;and the G6 group also showed a rebound in hepatic glycogen level compared with the G4 group.Conclusion: Cigarette smoking can significantly aggravate the disorder of glucose and lipid metabolism in diabetic mice.Andrographolide has obvious antagonistic effect on this effect.
Keywords/Search Tags:Male, Smoking, Dyslipidemia, Hyperglycemia, Diabetes, Andrographolide, Cigarette smoke, Intervention effect
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