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Expression Of Cytokines In Diabetic Kidney Disease And Renal Protective Effect Of Astragalus IV

Posted on:2017-04-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:W J WangFull Text:PDF
GTID:1224330488954023Subject:Internal medicine of traditional Chinese medicine
Abstract/Summary:PDF Full Text Request
Objective1 To explore the characteristics of traditional Chinese medicine in the treatment of DKD;2 To observe the expression of serum CXCL12 cytokines in DKD patients of deficiency of both qi and Yin with blood stasis;3 To observe the renal protective effect of AS-Ⅳ on type 2 diabetes db/db mice.Methods1 Literature ResearchUse the method of text mining to explore the characteristics of traditional Chinese medicine in the treatment of DKD. First establish key words list, and search of traditional Chinese medicine treatment of DKD theory study, experience summary, clinical trial related literatures. Establish a database with those literatures, use the keywords list search the database, picking up the keywords in database and save it. Keywords extraction by Cytoscape software in the network analysis, summarize the characteristics of medication.2 Clinic ResearchReference related literature to establish the diagnosis and the inclusion and exclusion criteria, the January March 2015 to 2016 in Guangzhou University of traditional Chinese Medicine Affiliated Shenzhen Hospital of traditional Chinese medicine outpatient and inpatient treatment in patients with DKD were selected into conforms to the standard of Qiyinliangxu stasis type 2 diabetes nephropathy patients were observed. The observation content included general information, the level of biochemical indexes and the expression of related cytokines.3 Vivo ResearchBased on above the results of the two studys, the db/db type 2 diabetic mice were treated with traditional Chinese medicine of astragaloside. During the course of medication, metabolic cages, blood glucose meter and application of noninvasive blood pressure measurement in animal metabolism index, blood glucose and blood pressure. After 12 weeks of treatment. Kill mice, blood and urine. Application of mouse renal function, serum albumin automatic biochemical analyzer to detect the biochemical indexes of mice were detected by ELISA; urinary albumin excretion rate and renal tubule injury index; application of PAS staining by electron microscopy of glomerulus and renal tubule pathological and ultrastructural injury; by immunoblotting (Western Blot) expression in kidney P-Akt and P-NF-kappa B protein detection.Results1 Literature ResearchThrough the retrieval of CNKI, a total of TCM treatment of DKD theoretical research, experience summary and clinical trials of a total of 3778 articles. After the screening,58 papers were obtained from theoretical research,264 literatures were summarized, and 618 clinical trials were summarized. After the conversion of these documents to the format of keyword extraction, get the key one dimensional frequency and two-dimensional frequency results, and use Cytoscape software to extract the results of network analysis. In the theoretical literature, the frequency of use is in the top three Chinese medicine prescription for Shenqi Pill, Shengmaisan, Jinkui Shenqi Pill, frequency of use in the top three Chinese medicine Astragalus, Salvia miltiorrhiza, tuckahoe. Network analysis found that the theoretical study, astragalus, salvia in the core position of the whole drug, and other drugs linked to the most. Experience summary of literature Chinese agent living in the top three is Zhenwu Decoction, bolus of 6 flavour glutinous rehmannia, Poria five powder, network analysis results found Zhenwu Decoction and the top ten other prescriptions almost all exist the United, and economic students Shenqi Pill, Jinkui Shenqi Pill, Liuwei Dihuang pill, Shengmaisan closely, and other prescription is relatively independent. The results showed that the first three were astragalus root, red sage root and root, and the network analysis showed that Astragalus and Radix were located in the center of the drug application. Clinical trials of Chinese agent mining results of three respectively Liuwei Dihuang pill, Yang also five soup, Zhenwu Decoction, network analysis results Jinkui Shenqi Pill, Liuwei Dihuang pill is in the core position. The results of the first three units of the traditional Chinese medicine data mining are astragalus root, red sage root and root, and the network analysis results show that the astragalus root is still in the core position of the medicine.2 Clinic ResearchA total of 80 cases of outpatient and inpatient cases in Shenzhen Chinese Traditional Medical Hospital affiliated to Guangzhou University of Chinese Medicine from March 2015 to January 2016 were included in this study, and 21 healthy people were included in the physical examination clinic as a control group. All cases included points for normal group (n= 21),19 cases of diabetes mellitus group (DM group) and DKD stage 1 to 2 groups (DN1-2 group) 19, the 3rd stage of DKD group (DN3 group, n= 20), DKD stage 4 group DN4 group (21 cases), DKD (DN) 5 period group (dn5 group) 21 cases. There was no significant difference in age, sex, weight and other basic data between the groups. But BMI, blood pressure, blood glucose and glycosylated hemoglobin index in the N group was significantly lower than the DN group. Renal function, SCr from the N group to the DN5 group of patients gradually increased, BUN content of DN4, the highest level of the 5 groups, GFR levels in the early stage of DKD increased, the latter gradually decreased, at the end of the approach to the minimum. In addition to HDL, lipid metabolism, the results of the group were more consistent, the HDL level of N group was significantly higher than other groups. CXCL12 detection results, N group and DN5 group were the highest, DM group was the lowest, and the difference between the N group and the group was statistically significant. The content of MCP-1 in the DN4 and the 5 groups was the highest, and the difference was statistically significant between the N group and the group. TGF-beta 1 test results show that the DKD group is higher than the N group. CRP demerit display, N group and DN5 group was the lowest, while the other DKD groups and N group differences were statistically significant.3 Vivo ResearchIn vivo Research, db/db mice were randomly divided into model group and treatment group, with 8 mice in each group. The treatment group was treated with Astragaloside IV for 12 weeks.8 db/m mice were used as the control group. Model group and treatment group were significantly higher than the normal group, model group and body weight increases faster than the treatment group. At the end of the experiment, the model group blood pressure lower than the normal group, and the blood pressure in the treatment group were significantly increased, and was significantly higher than the model group, the difference was statistically significant. Reduce the heart rate of treatment group compared with the model group, the difference was statistically significant. Model group and treatment group mice left and right kidney weight was higher than the normal value, the difference was statistically significant in model group and normal group, and treatment group was no significant difference.In terms of blood glucose and glycosylated hemoglobin, model group and treatment group were much higher than the normal group, but there was no significant difference between the treatment group and the model group. Mice UAE, model group, treatment group were higher than the normal group. The content of urinary albumin in the treatment group was lower than that in the model group, and there was significant difference between the two groups at eighth and twelfth weeks.Biochemical indicators, in addition to SCr, TG, LDL, the other indicators of the model group were higher than the normal group, and the difference was statistically significant. Except TC, HDL and NAG, the results of the treatment group were compared with the model group, and the difference was statistically significant.The pathological changes of mice in the model group, the glomerular and tubular hypertrophy, the increase of FPW, GBM and TBM were compared with the normal group, the difference was statistically significant. The treatment group can reduce glomerular and renal tubule area, inhibition of GBM and TBM increased. Foot process width, the model group was the highest, compared with the normal group, much higher than the normal group. The treatment group was lower than that of model group, and there was significant difference compared with the model group.Pathway proteins, p-Akt results showed that the model group compared with the normal group, the treatment group had statistical significance. The expression results of NF- p- kappa p65 B were consistent with p-Akt.In db/db, the expression of TGF-in urine of ELISA model group was much higher than that in the normal group, and the difference was significant between the treatment group and the treatment group. Mouse kidney TGF-beta 1 treatment group was far lower than the normal group and model group, and the difference was statistically significant. NGAL results showed that the model group was the highest in mice, the treatment group was lower than the model group, and the difference was statistically significant. KIM-1 results model group was higher than the treatment group, and the difference was statistically significant.Conclusion1 Chinese medicine Astragalus is one of the core of traditional Chinese medicine treatment of DKD;2 The relationship between disease and metabolic disorder, abnormal hemodynamics in DKD patients is closely. In deficiency of both qi and Yin with blood stasis type DKD, increased inflammatory factor expression in serum of patients had to do with progression of disease.3 The single extract of Astragalus has protective effect on the kidney of type 2 diabetic db/db mice. By inhibiting the activation of Akt/NF- nuclear factor kappa db/db in the kidney of B mice, the effect of the serum albumin in db/db mice can be reduced by reducing the kidney damage.
Keywords/Search Tags:Text mining, deficiency of both qi and yin, CXCL12, Astragaloside Ⅳ, Akt/NF-κB
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