Dissertation > Excellent graduate degree dissertation topics show

Effect of the Combination of Enalapril with Mycophenolate Mofetil on Expression of Connective Tissue Growth Factor in the Kidney in Diabetic Rats

Author: BaiYouWei
Tutor: WuYongGui
School: Anhui Medical University,
Course: Internal Medicine
Keywords: Diabetes Kidney Enalapril Mycophenolate mofetil Connective tissue growth factor
CLC: R587.2
Type: Master's thesis
Year: 2007
Downloads: 56
Quote: 0
Read: Download Dissertation

Abstract


Background and Objective Diabetic nephropathy is a major complication of diabetes and a leading cause of end-stage renal failure in many developed and developing countries. The developmental and progressive mechanism of diabetic nephropathy include an activated rennin-angiotensin system (RAS), accumulation of advanced glycation end-products, an activated polyols pathway, oxidative stress and dyslipidaemia. The induction of cytokines such as transforming growth factorβ1 is also important. Connective tissue growth factor (CTGF) a downstream mediator of TGFβ,that is the most important pro-sclerosis growth factors. Diabetic nephropathy is generally considered a nonimmune disease; however, examination of human biopsies and animal models has shown the presence of accumulation of macrophages and overexpression of leukocyte adhesion molecules and chemokines in diabetic kidneys. It was shown that treatment with angiotensin renin-angiotensin system (RAS) blockade as angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) or anti-inflammatory drugs as mycophenolate mofetil (MMF) and mizoribine attenuated renal injury in the diabetic rats. However, renal protection with either ACE inhibitor or MMF as monotherapy is suboptimal. We previously reported that the combination of enalapril (an ACE inhibitor) and MMF confers superiority over monotherapies on renoprotection. Our present study is to investigate whether RAS blockade combined with anti-inflammatory drugs have additional effects against the expression of CTGF in the kidney in diabetic rats. Methods Diabetes was induced by injection of streptozotocin after uninephrectomy. Rats were randomly separated into five groups: control (C), diabetes (DM), diabetes treated with enalapril (DM+E, an ACE inhibitor, 10 mg/kg/d by gastric gavage), diabetes treated with MMF (DM+MMF, 10mg/kg/d by gastric gavage), or diabetes treated with a combination of both agents (DM+E+MMF) and were followed for 8 weeks.24 h urinary albumin excretion rate (AER) and renal tissue morphology were observed by light microscopy after 8 weeks. Expression CTGF protein was performed by immunohistochemistry method in the kidney.Results 1.clinical and metabolic parameters: Rats in DM group had reduced body weight gain and increased blood glucose level. No effects on body weight and blood glucose were observed with monotherapy treatment or enalapril and MMF combination. Kidney enlargement was observed in DM group, which was significantly reduced by treatment with enalapril or MMF and further lowered by the combination of the two. 2. albumin excretion rate (AER):In DM group, albuminuria was significantly increased when compared to C group, treatment with enalapril or MMF attenuated the increase in albuminuria in the diabetic rats, but this level was still higher than that observed in control rats, the combination of enalapril and MMF was associated with a further reduction in albuminuria than was seen with either drug administrated alone, the similar AER level to that observed in control animals. 3.Renal histology: Rats in group DM had an increase in the glomerular volume when compared with the values in group C. Enalapril or MMF treatment ameliorated the increase of the glomerular volume, and the combination of the two was associated with further reduction in glomerular volume. Rats in group DM had an increase in the tubulointerstitial injury index when compared to group C, enalapril or MMF treatment was associated with a reduction in tubulointerstitial injury index as compared with group DM, but this did not reach statistical significance. The combination of the two was associated with a reduction in tubulointerstitial injury index as compared with group DM. 4.Renal CTGF expression: In the kidneys of group C, there was minimal staining for CTGF, diabetes was associated with a prominent increase in renal CTGF immunostaining, which was seen in glomeruli and tubulointerstitium, enalapril and MMF treatment reduced overexpression of CTGF in the glomeruli as well as in the tubulointerstitium, which nearly completely abrogated by combination therapy.Conclusion The combination of enalapril and MMF confers superiority over monotherapies on renoprotection, which mechanism may be at least partly correlated with synergetic suppression on overexpression of CTGF.

Related Dissertations

  1. To Observe the Clinnical Effect of Bu Shen Huo Xue Haustus Treating Kidney-Asthenia and Blood Stasis of Old Patients with Hypertension,R259
  2. The Clinical Study of Bianmi Ⅰ Hao on Constipation Complicated by Hemodialysis for Spleen-Kidney Deficiency and Dampness Originating from Interior,R259
  3. Serum A-FABP Levels and Its Expression in Atherosclerotic Plaques of Diabetes Mellitus,R587.1
  4. Construction of Stably Transfected HEK-293 Cell Line Expressing Human OATP1B1-wild/Variant Alleles,R96
  5. Bing- thick academic thought and clinical experience and empirical studies apply to turtle soups treatment of chronic kidney disease,R249.2
  6. Multi-center Study of Early Hemofiltration Treat Sepsis Associated AKI,R692.5
  7. Professor Liu Yanchi academic thought and clinical experience and clinical studies for treatment of diabetes,R249
  8. Common TCM syndrome and serum homocysteine ??and diastolic function relationships of the newly diagnosed patients with type 2 diabetes,R259
  9. The Effect and Pharmacological Analysis of Houttuynia Cordata Thunb (HCT) on Diabetes Mellitus,R285.5
  10. Effect of High Glucose on Chemokine Ligand 16 (CXCL16) Expression and Secretion in THP-1 Macrophages and Intervention of Aspirin in the Activity,R587.2
  11. The Effect and Mechanism of p38MAPK Inhibitor CBS3830 on Intimal Hyperplasia in Autogenous Vein Grafts of Diabetic Rats,R587.1
  12. Study on Configuration, Function and Histopathology of Compensatory Kidney in Dog,S858.292
  13. Effect of β-Casomorphin7 or Casein Peptides on Blood Glucose and Oxidative Stress of the Diabetic Rats,R587.1
  14. Experimental Study of Influence of Atrovastatin on Expression of NF-κB in Retionpathy of Diabetic Rats,R587.1
  15. Relationship between Level of Serum Uric Acid and Lower Extremity Arterial Disease in Patients with Type 2 Diabetes Mellitus,R587.1
  16. Improvement of Interleukin Profiles in Patients with Type 2 Diabetes Mellitus After Add-on Acarbose Therapy Independent of Glycemic Control,R587.1
  17. Efficacy and Safety of Biphasic Insulin Aspart 30 Once-daily Treatment in Patients with Type 2 Diabetes,R587.1
  18. The Blood Glucose Control and Influencing Factors in Type 2 Diabetic Patients with Oral Hypoglycemic Agents,R587.1
  19. The Analysis of Related Factors in Type 2 Diabetes with Depression,R587.1
  20. Effect of β-Casomorphin-5 on Blood Glucose and Oxidative Stress of Diabetic Rats,R587.1
  21. The Analysis of the Disease Constituent Ratio in 1130 Inpatients of the Department of Nephrology,R692

CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetic coma and other complications
© 2012 www.DissertationTopic.Net  Mobile