BackgroundDiabetic cardiomyopathy (CMP) is a common and disabling disease in diabetic patients, however no effective treatments have been developed. Although granulocyte-colony stimulating factor (G-CSF) improves heart function in myocardial infarction, its effect on non-ischemic CMP such as diabetic CMP is unknown. In the present study, we investigated the effects of G-CSF on diabetic CMP in a rat model of type II diabetes.MethodsTwenty 7-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF: a rat model of diabetes) rats and 10 male Long-Evans Tokushima Otsuka (LETO: normal controls) rats were used. All of the LETO and 8 OLETF rats were fed on tap water while the rest were fed on sucrose-containing water. After 10 weeks, saline or recombinant human G-CSF (100 μg/kg/day) was injected intraperitoneally for 5 days. Blood levels of glucose, total cholesterol and triglyceride, and Doppler echocardiograms for diastolic dysfunction were obtained just before and 4 weeks after the saline or G-CSF treatment. Light microscopy, electron microscopy (EM) and immunohistochemistry for transforming growth factor-β were employed to examine myocardial histology 4 weeks after the saline or G-CSF treatment.ResultsDiastolic dysfunction developed at 17 weeks (before the saline or G-CSF treatment) in the OLETF rats whether or not they were fed sucrose water, but were more severe in those fed sucrose water. Four weeks after saline or G-CSF treatment, diastolic function had recovered in the G-CSF-treated group regardless of sucrose water feeding, and perivascular and/or interstitial fibrosis in the G-CSF-treated group had decreased significantly. TGF-β immunoreactivity in the interstitial and perivascular tissue was also reduced in the G-CSF-treated group, and EM studies revealed less severe disruption of myofilaments and mitochondrial cristae, and decreased collagen deposition.ConclusionsG-CSF can ameliorate cardiac diastolic dysfunction and morphological damage, especially fibrosis of the myocardium, in OLETF rats with diabetic CMP.

Granulocyte-colony stimulating factor (G-CSF) is widely known to have a neuroprotective effect, but its effects on function and morphology in mechanical nerve injury are not well understood. The aim of this study was to confirm the time course of the functional changes and morphological effects of G-CSF in a rat model of nerve crush injury. Twelve-eight rats were divided into three group: sham-operated control group, G-CSF-treated group, and saline treated group. 2 weeks after the nerve crush injury, G-CSF was injected for 5 days. After 4 weeks, functional tests such as motor nerve conduction velocity (MNCV), mechanical and cold allodynia tests, and morphological studies were performed. G-CSF-treated rats had significantly improved nerve function including MNCV and mechanical and cold allodynia. In addition, G-CSF-treated rats had significantly higher the density of myelinated fibers than saline-treated rats. In conclusion, we found that 100 μg/kg administration of G-CSF promoted long-term functional recovery in a rat model of nerve crush injury.