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Study On The Action Mechanism Of Puerarin On Vascular Endothelial Function In Diabetic Mice

Posted on:2021-04-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:M ChenFull Text:PDF
GTID:1484306038975489Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Objective:With the improvement of people's living standards and lifestyle changes,the prevalence of diabetes continues to rise,becoming one of the major public health problems in the world.Diabetes is one of the independent risk factors for cardiovascular and cerebrovascular accidents.Diabetes patients have twice the risk of cardiovascular and cerebrovascular diseases than non-diabetic patients.Post-diabetes complicated with cardiovascular and cerebrovascular complications,such as stroke and coronary heart disease,are the main causes of diabetes death and disability,which bring a great burden to the social economy and people's lives.At present,the treatment of diabetic cardio-cerebrovascular accidents includes controlling blood sugar,controlling blood pressure,lowering blood lipids,anti-platelet aggregation,and protecting vascular endothelial function,and mainly controls blood sugar.However,there is currently no reliable evidence that strict blood sugar control can reduce the risk of diabetes complicated with cardiovascular and cerebrovascular accidents.In recent years,vascular endothelial dysfunction has received more and more attention as one of the major pathological changes after diabetes.Vascular endothelial dysfunction is common in diabetes and is closely related to target organ damage after diabetes.Vascular endothelial dysfunction can cause vasomotor dysfunction,platelet aggregation,vascular inflammation,etc.,which is the starting link of cardiovascular and cerebrovascular accidents.The therapeutic mechanism of motherland medicine on diabetes has the characteristics of multiple links and multiple targets,and it has certain advantages in preventing and treating cardiovascular and cerebrovascular complications after diabetes.Therefore,based on data mining,this topic(1)firstly sorted out the modern literature on the treatment of diabetes by traditional Chinese medicine,selected high-frequency traditional Chinese medicine for treatment of diabetes,and analyzed the clinical medication rules of diabetes to provide a further discussion on the prevention and treatment strategies of traditional Chinese medicine for diabetes New direction;(2)Based on the in vitro vascular tension detection technology,the main effective component of Pueraria lobata was experimentally studied,and the protective effect of Pue on vascular endothelium of diabetes was explored from the perspective of EDC,providing a theoretical basis for the clinical application of Pue.Methods:Literature research:A computer was used to search the Chinese Journal Full-text Database(CNKI)for the relevant literature on the treatment of diabetes by traditional Chinese medicine.EndNote was imported and EndNote was used to check the literature.After reading the topic abstract,manually select the documents that meet the inclusion criteria,download the documents and read the full text to further filter the documents.Finally,extract the document elements,use Excel in Microsoft office 2016 to record the document elements,and use SPSS 26.0 to analyze the data.Association rule analysis uses the Apriori algorithm,cluster analysis uses the inter-group connection method(Between-groups linkage)in system clustering,and the distance measurement method is Euclidean distance.Experimental research:(1)Apply N?-nitro-L-arginine methyl ester hydrochloride(L-NAME)to pre-treat the normal carotid artery vascular ring for 30 minutes,and then use Acetylcholine(ACh)EDC was induced in the common carotid artery of endothelial intact and endothelial-free mice,respectively.40 minutes before the addition of ACh,puerarin(Puerarin,Pue)and other inhibitors were used to pretreat the vascular ring to detect isolated vascular tone.Subsequently,normal C57BL/6 mice were injected intraperitoneally with Pue for 7 days and 14 days,respectively,and the isolated carotid artery was isolated to detect the changes of isolated endothelial Dependent Contraction(EDC)according to the previous method;(2)Build a mouse model of Type 2 Diabetes Mellitus(T2DM)by using a high-fat diet for three weeks plus streptozotocin(50mg/kg/d)for one week of continuous intraperitoneal injection.T2DM mice are randomly divided into model groups and In the treatment group,Pue 50mg/kg intraperitoneal injection was given to the treatment group,and a blank control group was set up.The first part method was used to detect the changes of ACh-induced EDC and ACh-induced carotid artery prostaglandins in each group.Results:The first part:1)Statistics of frequency of use of traditional Chinese medicine:Chinese medicines with a frequency of ?20 have 32 flavors,and the top 5 flavors with the highest frequency are astragalus,salvia miltiorrhiza,Ophiopogon japonicus,pueraria lobata,and rhizoma coptidis;2)drug-flavored taste and meridian statistics:Siqi Neutral cold(842 times)and sexual temperature(505 times)have the highest frequency,followed by sexual flatness(282 times),again sexual coolness(116 times)and sexual heat(18 times);the top three of Wuwei from high to The lowest order is sweet(1081 times),bitter(911 times),spicy(440 times),miso acid(150 times)and bitter(115 times).In terms of menstruation,Chinese medicine is used most frequently in the lung(857 times)and liver(850 times),followed by Chinese medicine in the spleen(761 times),stomach(662 times),heart(613 times)and kidney(499 times);3)Statistics of Chinese medicine categories:The first three categories are Qi-invigorating medicine(271 times),Yin-invigorating medicine(192 times)and Huoxue regulating menstruation medicine(172 times).In addition,deficiency medicines,including Qi-invigorating medicine,blood-enriching medicine,Yin-invigorating medicine and Yang-invigorating medicine,have a total frequency of 575 times and a frequency of 32.4%.Heat-clearing medicines,including heat-clearing blood-cooling medicines,heat-clearing purgative powders,heat-clearing dampness medicines,and heat-deficiency medicines,with a total frequency of 414 times and a frequency of 23.4%;4)Analysis of high frequency Chinese medicine association rules:a total of 10 sets of dual medicines were obtained And 27 sets of triple drug pairs.According to the frequency,the high-frequency dual drug pair is Danshen+Astragalus,Red Peony+Salvia,Chuanxiong+Danshen and Chuanxiong+Astragalus,Radix Scutellaria+Coptis chinensis,Codonopsis+Astragalus,Huang Jing+Danshen,Atractylodes+Astragalus,Wolfberry+Salvia and Radix Dragon+Astragalus.The top 10 high-frequency triple drugs are red peony+astragalus+salvia,schisandra+astragalus+Ophiopogon japonicus,red peony+Ophiopogon japonicus+Danshen,Chuanxiong+Ophiopogon japonicus+ Astragalus,Astragalus+Astragalus+Salvia,Chuanxiong+Pueraria Root+ Astragalus,Codonopsis+Ophiopogon+Astragalus,Scrophulariaceae+Trichosanthin+Ophiopogon japonicus,Red Peony+Pueraria Root + Salvia miltiorrhiza,Scrophulariaceae+Zhimu+Ophiopogon japonicus.5)Five meaningful clustering groups were obtained,namely Codonopsis pilosulae,Radix ginseng,Astragalus,licorice,ginseng,wolfberry,Huang Jing,Pueraria lobata,Ophiopogon japonicus,trichosanthin,Anemarrhena,Scrophulariaceae,Scrophulariaceae,Habitat,Alisma,Schisandra Atractylodes,Atractylodes,Angelica,Safflower,Chuanxiong,Salvia,Red Peony,White Peony,Leech,Earth DragonDogwood;Coptis chinensis,Scutellaria baicalensis.Part ?:Experiment 1:1)The mouse carotid artery EDC is mediated by cyclooxygenase and TP receptors;2)COX-2 but not COX-1 mediates the mouse carotid artery EDC;3)Pue It can inhibit the carotid artery EDC in mice;4)Pue can inhibit the release of endothelium-derived contractile factor prostaglandins.Experiment 2:1)ACh only causes the endothelial intact vasoconstriction and can be used by the non-selective cyclooxygenase(COX)inhibitor indomethacin(3 ?mol/L)or thromboxane-prostaglandin receptor(Thromboxane-Prostanoid Receptor(TP receptor)antagonist S18886(30nmol/L)inhibits.Pue 40 minutes pretreatment can effectively inhibit EDC,but does not affect the contraction induced by U46619.Continuous intraperitoneal injection of 50 mg/kg for 14 days in mice can significantly inhibit ACh-induced EDC;2)Pue 50 mg/kg intraperitoneal injection can significantly inhibit the content of EDC and prostaglandins in T2DM mice,but it has no effect on the contraction of vascular smooth muscle,and Can not improve the body weight and blood sugar of T2DM mice.Conclusion:1.The high-frequency medications for diabetes and its cardiovascular and cerebrovascular complications are astragalus,salvia miltiorrhiza,Ophiopogon japonicus,pueraria lobata,and rhizoma coptidis,mainly based on the traditional Chinese medicines for invigorating qi,invigorating yin and clearing heat and promoting blood circulation.2.Pue could inhibit the carotid EDC of T2DM diabetic mice,the mechanism may be to inhibit the release of prostaglandins.
Keywords/Search Tags:Chinese medicine, diabetes, puerarin, vascular endothelial dysfunction
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