Nerve growth factor(NGF) is closely ralated to the occurrence and development of diabetic peripheral neuropathy (DPN). Traditional Chinese medicine has certain effects on the promotion of NGF expression. It analyzes the relationship of NGF and DPN and the effects of Traditional Chinese Medicine on them as well as the existing problems and looks into the future research in this domain.
Animals ; Diabetic Neuropathies ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Gene Expression ; drug effects ; Humans ; Nerve Growth Factor ; genetics ; metabolism

OBJECTIVETo investigate the content of nerve growth factor (NGF) in penis of rats with diabetic erectile dysfunction (DED) and apply rhNGF to treat the DED rat model to study the pathogenesis mechanism of DED and treatment effects by NGF for DED rat model.

METHODSFifty adult male SD rats were randomly selected to make up diabetic models. After 8 weeks, the mRNA and protein levels of NGF in rat penis were detected. Then the rest of rats were divided into 5 groups: normal control group, non-treated diabetes group, NGF treatment group, insulin treatment group, NGF plus insulin treatment group. After 8 weeks of treatment, intracavernous pressure (ICP) was measured. The content of neuronal nitric oxide synthase (nNOS) in the erectile tissue was also value- ated by immunohistochemistry staining.

RESULTSCompared with those of normal control group, the mRNA content of NGF and protein in the penis of non-treated diabetic rats is increased significantly. Compared with non-treated diabetic group, ICP was much higher in the treated groups which received NGF or/and insulin therapy, and the changes in nNOS staining of those groups were the same.

CONCLUSIONThe injury of pelvic splanchnic nerves in advanced stage of diabetes may lead to DED, which may be relevant to the abnormal of NGF level or the NGF receptors. The increased extent of NGF in penis of rat with DED suggests that erectile nerves be severely damaged by diabete and the increase of producing NGF couldn't compensate the needs for reproduction of the nerve fibers. The ability of combination of NGF with its receptor may also be damaged. It is helpful to use exogenous NGF to lessen the partly neuropathy and improve the erectile dysfunction of diabetic rats. The abnormal of NGF may play an important role in the pathogenesis of diabetic ED and its treatment.

Animals ; Diabetes Mellitus, Experimental ; complications ; Erectile Dysfunction ; drug therapy ; etiology ; metabolism ; Male ; Nerve Growth Factor ; biosynthesis ; genetics ; therapeutic use ; Penis ; metabolism ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the effect of xiaokeling concentration fluid on insulin-like growth factor-1 (IGF-1) mRNA expression in sciatic nerve of Streptozotocin-induced diabetic rats. METHODS: Thirty diabetic rats were randomly divided into model group, mecobalamin tablets group, and xiaokeling concentration fluid group. The IGF-1 mRNA level in sciatic nerve of each group was determined after 8 weeks by relative quantity RT-PCR. RESULTS: The IGF-1 mRNA level in sciatic nerve of diabetic rats between xiaokeling concentration fluid group, mecobalamin tablets group and normal group showed no significant difference ( P = 0.213, P = 0.822, P = 0.304 ), while was significantly higher than that of the model group ( P < 0.05 ). IGF-1 mRNA level was negatively correlated with the level of blood sugar (P < 0.05). CONCLUSION IGF-1 mRNA level decreased in sciatic nerve of diabetic rats. Xiaokeling concentration fluid can increase the IGF-1 mRNA level in sciatic nerve of diabetic rats. Xiaokeling concentration fluid is involved in the regulation of IGF-1 expression, and probably prevents diabetic peripheral neuropathy from deteriorating.
Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetic Neuropathies ; prevention & control ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Insulin-Like Growth Factor I ; biosynthesis ; genetics ; Male ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Receptor, IGF Type 1 ; Reverse Transcriptase Polymerase Chain Reaction ; Sciatic Nerve ; metabolism

BACKGROUNDWe hypothesize that increased atrial oxidative stress and inflammation may play an important role in atrial nerve sprouting and heterogeneous sympathetic hyperinnervation during atrial fibrillation (AF). To test the hypothesis, we examined whether the antioxidant and anti-inflammatory treatment with probucol attenuates atrial autonomic remodeling in a canine model of AF produced by prolonged rapid right atrial pacing.

METHODSTwenty-one dogs were divided into a sham-operated group, a control group and a probucol group. Dogs in the control group and probucol group underwent right atrial pacing at 400 beats per minute for 6 weeks, and those in the probucol group received probucol 1 week before rapid atrial pacing until pacing stopped. After 6-week rapid atrial pacing, general properties including left atrial structure and function, atrial hemodynamics and the inducibility and duration of AF were measured in all the groups. Atrial oxidative stress markers and serum C-reactive protein (CRP) concentration were estimated. The degree of nerve sprouting and sympathetic innervation at the right atrial anterior wall (RAAW) and the left atrial anterior wall (LAAW) were quantified by immunohistochemistry, atrial norepinephrine contents were also detected. Atrial beta-nerve growth factor (beta-NGF) mRNA and protein expression at the RAAW and LAAW were assessed by real-time quantitative RT-PCR and Western blotting respectively.

RESULTSAtrial tachypacing induced significant nerve sprouting and heterogeneous sympathetic hyperinnervation, and the magnitude of nerve sprouting and hyperinnervation was higher in the RAAW than in the LAAW. Atrial beta-NGF mRNA and protein levels were significantly increased at the RAAW and LAAW, and the upregulation of beta-NGF expression was greater at the RAAW than at the LAAW in the control group. The beta-NGF protein level was positively correlated with the density of sympathetic nerves in all groups. Probucol decreased the increase of CRP concentration and attenuated atrial oxidative stress caused by atrial tachypacing. In addition, probucol could effectively inhibit atrial beta-NGF upregulation, significantly attenuate atrial nerve sprouting and heterogeneous sympathetic hyperinnervation, and dramatically reduce the inducibility and duration of AF.

CONCLUSIONSThe atrial over-expression of beta-NGF possibly caused by increased oxidative stress and inflammation may be the main mechanism underlying atrial autonomic remodeling during AF. Probucol attenuates atrial autonomic remodeling possibly by its antioxidant and anti-inflammatory actions.

Animals ; Antioxidants ; therapeutic use ; Atrial Fibrillation ; drug therapy ; Blotting, Western ; C-Reactive Protein ; metabolism ; Cardiac Pacing, Artificial ; adverse effects ; Disease Models, Animal ; Dogs ; Electrocardiography ; Female ; Heart Atria ; Immunohistochemistry ; Male ; Nerve Growth Factor ; genetics ; metabolism ; Norepinephrine ; metabolism ; Probucol ; therapeutic use ; Reverse Transcriptase Polymerase Chain Reaction

Due to the therapeutic potential of gene therapy for neuronal injury, many studies of neurotrophic factors, vectors, and animal models have been performed. The presumed dog beta-nerve growth factor (pdbeta-NGF) was generated and cloned and its expression was confirmed in CHO cells. The recombinant pdbeta-NGF protein reacted with a human beta-NGF antibody and showed bioactivity in PC12 cells. The pdbeta-NGF was shown to have similar bioactivity to the dog beta-NGF. The recombinant pdbeta-NGF plasmid was administrated into the intrathecal space in the gene therapy group. Twenty-four hours after the vector inoculation, the gene therapy group and the positive control group were intoxicated with excess pyridoxine for seven days. Each morning throughout the test period, the dogs' body weight was taken and postural reaction assessments were made. Electrophysiological recordings were performed twice, once before the experiment and once after the test period. After the experimental period, histological analysis was performed. Dogs in the gene therapy group had no weight change and were normal in postural reaction assessments. Electrophysiological recordings were also normal for the gene therapy group. Histological analysis showed that neither the axons nor the myelin of the dorsal funiculus of L(4) were severely damaged in the gene therapy group. In addition, the dorsal root ganglia of L(4) and the peripheral nerves (sciatic nerve) did not experience severe degenerative changes in the gene therapy group. This study is the first to show the protective effect of NGF gene therapy in a dog model.
Amino Acid Sequence ; Animals ; Base Sequence ; CHO Cells ; Central Nervous System Diseases/chemically induced/therapy/*veterinary ; Cloning, Molecular ; Cricetinae ; Cricetulus ; Cytomegalovirus ; Dog Diseases/*chemically induced/therapy ; Dogs ; Female ; Gene Therapy/*veterinary ; Genetic Vectors ; Male ; Molecular Sequence Data ; Nerve Growth Factor/genetics/*metabolism/*therapeutic use ; Pyridoxine/*toxicity