ABSTRACT
AIM:To investigate the effects of ginsenoside Rg1 on the behavioral changes and the autophagy of hippocampal neurons of the rats with post-traumatic stress disorder (PTSD).METHODS:The Sprague-Dawley rats were randomly divided into 5 groups:control group, model group, fluoxetine group, low-dose ginsenoside Rg1 group and high-dose of ginsenoside Rg1 group.The combination of single prolonged stress and foot stock was performed to induce PTSD-like animal model.The rats in fluoxetine group was administered with fluoxetine by gavage at dose of 10 mg/kg for 21 d, while the rats in low and high doses of ginsenoside Rg1 groups were administered with ginsenoside Rg1 by gavage at doses of 20 mg/kg and 40 mg/kg for 21 d, respectively.The rats in control group and model group were both given saline by gavage for 21 d.The open-field test and stiff behavior test were used to examine the behavioral changes of the rats.The morphological structure and numerical changes of the hippocampal neurons were observed by Nissl-staining method.We adopted immunofluorescence labeling to observe the beclin 1 and LC3 positive hippocampal neurons and the levels of beclin 1 and LC3-Ⅱ/LC3-Ⅰratio in rat hippocampus.RESULTS:Compared with control group, decreased vertical movement time and horizontal movement time in open-field test and increased rate of stiff behavior in the stiff behavior test were observed in model group.Hippocampal neurons in model group were loosely arranged with vacuole-like structures and different degrees of cell shrinkage in contrast with control group.More beclin 1 and LC3 positive cells were identified, and higher protein levels of beclin 1 and ratio of LC3-Ⅱ/LC3-Ⅰ in model group were found as compared with control group.However, increase in movement in open-field test and decrease in stiff behavior were detected in the rats treated with low-and high-dose ginsenoside Rg1 as compared with the model rats.Meanwhile, vacuole structures, the numbers of beclin 1 and LC3 positive neurons, the protein expression of beclin 1 and LC3, and the total cell numbers were increased.Higher dose of ginsenoside Rg1 had more profound effects on these observed results.CONCLUSION:Ginsenoside Rg1 alleviates the abnormal behaviors in the PTSD rats, which might be related to the inhibition of abnormal autophagy of hippocampal neurons.
ABSTRACT
[ ABSTRACT] AIM:To observe the change of skin histology in diabetic rats and to investigate the possible me-chanism of c-Jun N-terminal kinase (JNK) protein in the dorsal root ganglion (DRG) during the process.METHODS:Diabetic animal model was established in the male SD rats by intraperitoneal injection of streptozotocin.Plantar skin speci-mens of the rats were collected from control group, DM 2-week group (DM2), DM 4-week group (DM4), and DM 8-week group ( DM8) .Immunohistochemical staining and HE staining were used to observe the change of PGP 9.5 immunoreactive nerve terminals and the structures of the skin tissues.The protein expression of PGP 9.5 in the plantar skin tissues, and JNK and p-JNK protein in the DRG within lumbar 5, 6 (L5, 6), and sacral 1 (S1) spinal cord segments were detected by Western blotting.RESULTS:PGP 9.5 immunoreactive nerve terminals of the plantar skin of the rats mainly distributed in the basal layer of the epidermis and papillary dermis.Compared with control group, PGP 9.5 positive nerve terminals in DM4 group showed reduced density and sparse distribution.PGP 9.5 positive nerve terminals in DM8 group showed signifi-cantly reduced distribution, thinner nerve diameter, shorter length and distorted shape.Histological changes of the thinner epidermal tissue, reduced epidermal cell layers, uneven cell distribution and arrangement in DM4 group, and significantly reduced epidermal cell layers, swollen and blurred cells, increasing cell gap, lack of stratified epidermis arrangement for part of epidermis, atropal and degenerated dermal collagen fiber, significantly decreased subcutaneous fat in DM8 group were observed.The results of Western blotting showed that the protein expression of PGP 9.5 in the plantar skin tissue of DM rats was progressively decreased along with the disease, while the protein level of p-JNK in L5, 6-DRG or S1-DRG showed a gradual increasing trend.PGP 9.5 immunoreactive positive nerve terminal density of plantar skin in DM rats had a negative correlation with the protein level of p-JNK in L5, 6-DRG and S1-DRG (P<0.01), but showed a significant positive correlation with the plantar skin thickness (P<0.01).CONCLUSION:The protein level of p-JNK within L5, 6-DRG or S1-DRG in DM rats shows a progressive enhancement.At the same time, there is a significant change in the skin tissue density and structure.The changes of skin tissue and nerve morphology in DM rat may be related to the activation of JNK/SAPK pathway in L5, 6-DRG or S1-DRG cells.Blocking or inhibiting JNK/SAPK pathway may delay the diabetic pe-ripheral neuropathy and reduce the risk of skin lesions.