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Pharmacodynamic Study On Peripheral Neuropathy In Type 2 Diabetic Rats And Chemical Composition Analysis Of Compound Long-qi Decoction

Posted on:2020-02-16Degree:MasterType:Thesis
Country:ChinaCandidate:Y HeFull Text:PDF
GTID:2404330578483525Subject:Pharmacognosy
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Compound Long-qi Decoction is a clinical prescription of traditional Chinese medicine.It eontains seven herbs,including Radix Astragali,Cinnamon Twig,Radix Paeoniae Rubrathe,Angelicae Sinensis Radix,Caulis Spatholobi,Pheretima and Ramulus Mori.The whole prescription has the effects of benefiting qi and replenishing blood,promoting blood circulation for removing obstruction in collaterals.It is used to treat diabetic peripheral neuropathy.This paper studies the pharmacodynamic effect of Compound Long-qi Decoction on diabetic peripheral neuropathy,and then explores its corresponding mechanism of action,and makes preliminary qualitative identification of the chemical constituents of Compound Long-qi Decoction.The details are as follows:(1)Effect of Compound Longqi Decoction on Peripheral Neuropathy in Type 2 Diabetic RatsWistar rats were fed with high-fat diet and STZ to induce type 2 diabetes mellitus.After 4 weeks of blood sugar stabilization,the rats were divided into model control group,positive control group,high-dose Long-qi Decoction group,medium-dose Long-qi Decoction group and low-dose Long-qi Decoction group according to blood sugar.Compound Long-qi Decoction was extracted in proportion to the prescription to prepare dry extract powder as the test substance,which was administered for 16 weeks.The levels of blood glucose and blood lipid were measured after 4 weeks of administration;and the viscosity of blood was measured at 5 and 9 weeks after treatment.The changes of behavior of rats were measured after administration for 14 weeks to 16 weeks.After the rats were executed,the serum blood sugar,glycosylated hemoglobin,blood lipid,SOD,MDA,T-AOC,GSH-Px biochemical indexes were determined.Pathological changes of retinal vascular network in rats revealed by PAS staining.The results showed that Compound Long-qi Decoction could slow down the decrease of sciatic nerve conduction velocity caused by diabetes mellitus(p<0.05),decrease GSH-Px and cholesterol in serum,decrease glycosylated hemoglobin,blood sugar and triglyceride in erythrocyte,but there was no significant difference between them.Retinopathological results showed that Compound Long-qi Decoction could improve the retina in different degrees.The pathological changes showed that Compound Long-qi Decoction was improved in different degrees of epineurium thickened lesions in rat model of nerve fibers,axonal degeneration of myelin disintegration,shedding;improved the pathological changes of retinal capillary thin state,reduce capillary hemangioma,slow decrease of endothelial cells.It can be concluded that Compound Long-qi Decoction has a certain effect on diabetic peripheral neuropathy.(2)To Investigat the Mechanism of Compound Long-qi Decoction to Improve Diabetic Peripheral NeuropathyThe content of sorbitol in sciatic nerve tissue and erythrocyte of rats was determined by pre-column Derivatization-High Performance Liquid Chromatography(HPLC).The results showed that compound Long-qi decoction could reduce the content of sorbitol in sciatic nerve tissue and erythrocyte of rats with diabetic peripheral neuropathy(p<0.01).The aldose reductase was extracted from rat lens tissue.The inhibition effect of compound Long-qi Decoction on aldose reductase activity in vitro was investigated through a set of enzymatic reaction system-The results showed that compound Long-qi decoction could inhibit aldose reductase activity at a certain concentration.In conclusion,Compound Long-qi Decoction can inhibit the activity of aldose reductase in diabetic rats and reduce the content of sorbitol in nerve tissue and erythrocyte.This may be the main way of Long-qi Decoction to improve diabetic peripheral neuropathy.(3)Chemical Composition Analysis of Compound Long-qi DecoctionUsing UPC/Q-TOF-MS technology to identify the main components of Compound Long-qi Decoction and its constituents,qualitatively identify the main components and some sources of compound Long-qi decoction for attribution.The result was that 70 chemical constituents of Compound Long-qi Decoction were identified,which 25 belong to Radix Astragali,5 belong to Cinnamon Twig,25 belong to Radix Paeoniae Rubrathe,8 belong to Angelicae Sinensis Radix,10 belong to Caulis Spatholobi,11 belong to Pheretima and 2 belong to Ramulus Mor:i.The results showed that Astragalus membranaceus and Radix Paeoniae Rubra played an important role in the prescription.In this paper,we explored the therapeutic effect of Compound Long-qi Decoction on diabetie peripheral neuropathy rats with the idea of holistic study.It was found that Compound Long-qi Decoction could improve the conduction function of sciatic nerve by inhibiting the activity of aldose reductase,reducing the content of sorbitol in tissues.In addition,Compound Long-qi Decoction improves retinal capillaries and tends to alleviate blood sugar,glycosylated hemoglobin and oxidative stress.Composition analysis of Compound Long-qi Decoction provides clues for the study of its pharmacodynamic material basis.This paper provides experimental data for the improvement of peripheral neuropathy in type 2 diabetes mellitus by Compound Long-qi Decoction,adds basic data for the multi-level and multi-target treatment of traditional Chinese medicine,and provides research data and new ideas for the development of new drugs.
Keywords/Search Tags:Compound Long-qi Decoction, Diabetic Peripheral Neuropathy, Diabetic Retinopathy, Aldose Reductase, UPLC/Q-TOF/MS
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