International Urology and Nephrology

, Volume 43, Issue 1, pp 109–116 | Cite as

Nerve growth factor and substance P: expression in a rat model of diabetic bladder

  • Yongzhi Li
  • Benkang Shi
  • Dan Wang
  • Ping Wang
  • Vincent Laudon
  • Jianping Zhang
  • Yili LiuEmail author
Urology – Original Paper



To evaluate the gene and protein expression of nerve growth factor (NGF) and substance P (SP) in the bladder 8 weeks after diabetes induction and investigate the pathogenesis of diabetic cystopathy.


Thirty Wistar rats were divided into three groups: control (n = 10), streptozotocin-induced diabetic group (n = 10) and Pygeum africanum (P. africanum) group (n = 10; diabetic rats were given P. africanum (100 mg/kg/day)). Eight weeks later, the bladders were dissected. We measured the expression of NGF and SP in the bladders using RT–PCR, ELISA and immunohistochemistry.


We found a significantly reduced expression of NGF in the bladders from the diabetic group compared with the control. Immunohistochemical studies showed a statistically significant reduction of SP in the bladders from the diabetic group compared with the control (P < 0.05). Expression of NGF was greatly increased in the P. africanum group compared with that of the diabetic group. Immunohistochemical studies showed an increased level of SP in the bladders from the P. africanum group compared with the control (P < 0.05).


Our findings indicated that the decrease in NGF and SP may be a contributory factor in diabetic cystopathy. In addition, P. africanum could significantly upregulate the expression of NGF and SP in diabetic rats.


Diabetic bladder Substance P Nerve growth factor Pygeum africanum 



This study was funded by Nature and Science Foundation of Shandong Province, China (No. Y2005C19). We thank Qu Xun from Clinical and Basic Laboratory, Qilu Hospital of Shandong University, Shandong Province, China for the RT–PCR and ELISA work.


  1. 1.
    Aloe L, Manni L, Properzi F, De Santis S, Fiore M (2000) Evidence that nerve growth factor promotes the recovery of peripheral neuropathy induced in mice by cisplatin: behavioral, structural and biochemical analysis. Auton Neurosci 86(1–2):84–93PubMedCrossRefGoogle Scholar
  2. 2.
    Andersson KE (2002) Bladder activation: afferent mechanisms. Urology 59(5 Suppl 1):43–50PubMedCrossRefGoogle Scholar
  3. 3.
    Apfel SC (1999) Neurotrophic factors in peripheral neuropathies: therapeutic implications. Brain Pathol 9(2):393–413PubMedCrossRefGoogle Scholar
  4. 4.
    Bjorling DE, Beckman M, Clayton MK, Wang ZY (2002) Modulation of nerve growth factor in peripheral organs by estrogen and progesterone. Neuroscience 110(1):155–167PubMedCrossRefGoogle Scholar
  5. 5.
    Boulbes D, Soustelle L, Costa P, Haddoum M, Bali JP, Hollande F, Magous R (2006) Pygeum africanum extract inhibits proliferation of human cultured prostatic fibroblasts and myofibroblasts. BJU Int 98(5):1106–1113PubMedCrossRefGoogle Scholar
  6. 6.
    Chiarelli F, Santilli F, Mohn A (2000) Role of growth factors in the development of diabetic complications. Horm Res 53(2):53–67PubMedCrossRefGoogle Scholar
  7. 7.
    Choo MS, Bellamy F, Constantinou CE (2000) Functional evaluation of Tadenan on micturition and experimental prostate growth induced with exogenous dihydrotestosterone. Urology 55(2):292–298PubMedCrossRefGoogle Scholar
  8. 8.
    Goins WF, Yoshimura N, Phelan MW, Yokoyama T, Fraser MO, Ozawa H, Bennett NJ, de Groat WC, Glorioso JC, Chancellor MB (2001) Herpes simplex virus mediated nerve growth factor expression in bladder and afferent neurons: potential treatment for diabetic bladder dysfunction. J Urol 165(5):1748–1754PubMedCrossRefGoogle Scholar
  9. 9.
    Kamata K, Inoue K, Kasuya Y (1993) Changes in contractile responses of the urinary bladder to substance P in streptozotocin-induced diabetic rats. Gen Pharmacol 24(3):547–553PubMedGoogle Scholar
  10. 10.
    Kaplan DR, Miller FD (2000) Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol 10(3):381–391PubMedCrossRefGoogle Scholar
  11. 11.
    Markle RA, Walker DK (1996) Effects of streptozotocin-induced diabetes and insulin treatment on substance P of the rat arterial wall. Life Sci 58(14):1123–1129PubMedCrossRefGoogle Scholar
  12. 12.
    Melo EA, Bertero EB, Rios LA, Mattos D (2002) Evaluating the efficiency of a combination of Pygeum africanum and stinging nettle (Urtica dioica) extracts in treating benign prostatic hyperplasia (BPH): double-blind, randomized, placebo controlled trial. Int Braz J Urol 28(5):418–425PubMedGoogle Scholar
  13. 13.
    Persson K, Andersson KE (1992) Nitric oxide and relaxation of pig lower urinary tract. Br J Pharmacol 106(2):416–422PubMedGoogle Scholar
  14. 14.
    Pittenger G, Vinik A (2003) Nerve growth factor and diabetic neuropathy. Exp Diabesity Res 4(4):271–285PubMedGoogle Scholar
  15. 15.
    Said G (2007) Diabetic neuropathy—a review. Nat Clin Pract Neurol 3(6):331–340PubMedCrossRefGoogle Scholar
  16. 16.
    Sasaki K, Chancellor MB, Phelan MW, Yokoyama T, Fraser MO, Seki S, Kubo K, Kumon H, Groat WC, Yoshimura N (2002) Diabetic cystopathy correlates with a long-term decrease in nerve growth factor levels in the bladder and lumbosacral dorsal root Ganglia. J Urol 168(3):1259–1264PubMedCrossRefGoogle Scholar
  17. 17.
    Tomlinson DR, Fernyhough P, Diemel LT (1997) Role of neurotrophins in diabetic neuropathy and treatment with nerve growth factors. Diabetes 46(Suppl 2):S43–S49PubMedGoogle Scholar
  18. 18.
    Tong YC, Hung YC, Lin SN, Cheng JT (1996) Alterations in urinary bladder synaptosomal neurotransmitter concentrations in two-week streptozotocin-induced diabetic rats. Neurosci Lett 206(2–3):165–168PubMedCrossRefGoogle Scholar
  19. 19.
    Wang D, Li Y, Hou G, Wang P, Zhang J, Laudon V, Shi B (2009) Pygeum africanum: effect on oxidative stress in early diabetes-induced bladder. Int Urol Nephrol. doi: 10.1007/s11255-009-9610-5
  20. 20.
    Yablonsky F, Nicolas V, Riffaud JP, Bellamy F (1997) Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts. J Urol 157(6):2381–2387PubMedCrossRefGoogle Scholar

Copyright information

© 747Springer Science+Business Media, B.V. 2010

Authors and Affiliations

  • Yongzhi Li
    • 1
  • Benkang Shi
    • 3
  • Dan Wang
    • 2
  • Ping Wang
    • 1
  • Vincent Laudon
    • 5
  • Jianping Zhang
    • 4
  • Yili Liu
    • 1
    Email author
  1. 1.Department of UrologyThe Fourth Hospital of China Medical UniversityShenyangChina
  2. 2.Institute of Experimental Nuclear MedicineShandong University School of MedicineJinanChina
  3. 3.Department of UrologyQilu Hospital of Shandong UniversityJinanChina
  4. 4.Department of PathologyQilu Hospital of Shandong UniversityJinanChina
  5. 5.Division of UrologyHartford HospitalHartfordUSA

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