Glutathione protects mitochondrion and alleviates liver ischemia-reperfusion injury in rats / 第二军医大学学报

Objective To investigate the protective effects of glutathione (GSH) against hepatic ischemia/reperfusion (I/R) injury and the related mechanism. Methods SD rats were randomized into Sham , I/R and GSH groups with 20 rats in each group. Rat models of segmental (70~Y) warm hepatic ischemia were established in I/R and GSH groups. GSH was injected through the femoral vein at the dose of 5 mg/kg 5 min before ischemia. At 24 h after reperfusion , liver injury was evaluated by serological and histological indices. Liver cell apoptoses were evaluated by TUNEL staining. The GSH/oxidized glutathione (GSSG) ratios of tissue level were compared between different groups. Liver mitochondria were collected and the mitochondrial calcium capacity (CRC) was evaluated. Results The serum aspartate transaminanse (AST) and alanine aminotransferase (ALT) levels in GSH group were significantly decreased 6 h after reperfusion compared with I/R group(P< 0. 05). 24 h after reperfusion , the liver injury was alleviated and the number of apoptosis cells was significantly decreased in GSH group compared with I/R group (P <0. 05). The GSH/GSSG ratio of tissue level in GSH group was significantly increased 6 h after reperfusion compared with I/R group (P<0. 05). Liver mitochondrial CRC in GSH group was significantly increased 6 h after reperfusion compared with I/R group (P<0. 05). Conclusion GSH preconditioning can protect liver from hepatic I/R injury, which is possibly by inhibiting oxidative response and subsequent inhibition of mitochondrial permeability transition.

Effect of Huannao Yicong prescription See Text extract on β-amyloid precursor protein metabolic signal transduction-related protein in brain tissue of dementia model transgenic mouse / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of Huannao Yicong Prescription (, HNYC, a Chinese medical compound) extract on β-amyloid precursor protein (APP) metabolic signal transduction related protein kinase C (PKC), tyrosine amyloid protein kinase (TrKA), and glycogen synthase kinase-3 (GSK-3) in brain tissue of transgenic mouse dementia model induced by APP.</p><p><b>METHODS</b>Sixty dementia model transgenic 3-month-old mice induced by APP695V717I were randomly allocated in four groups: the model group (A), the Donepezil (0.65×10(-3) g·kg(-1)·(-1))-treated group (B), and the two HNYC-treated groups (C and D) with high dosage (2.8 g·kg(-1)·(-1)) and low dosage (1.4 g·kg(-1)·(-1)) of HNYC extract, respectively, 15 mice in each group. Besides, a normal control group was set up with 15 C57BL/6J mice with the same age and genetic background as the model mice. The drugs for treatment were administered once a day by dissolving in equal-volume distilled water through gastric infusion, continued for 6 months, to mice in group A and to normal control group equal-volume distilled water was administered instead. Spatial learning and memory capacity of mice were observed by Morris water maze; their one-time escape response memory capacity was tested by diving platform; and changes of PKC, TrkA, and GSK-3 levels in hippocampus and cortex of brain were detected by Western blotting.</p><p><b>RESULTS</b>HNYC extract showed significant effects on increasing the time of model mice for swimming through the flat roof and the swimming time and path in the fourth quadrant P<0.05 or P<0.01). Diving platform test showed that the latent times in Groups B and C were longer than that in Group A significantly (P <0.05 and P<0.01). Compared with the normal control group, PKC and TrkA protein expression levels in hippocampus and cortex of model mice's brain lowered significantly (P<0.01), while GSK-3 protein expression increased significantly (P<0.01); compared with Group A (the model group), hippocampal and cortical levels of PKC protein expression in the intervened groups (B-D) as well as those of TrkA in Group C were higher (P<0.01 or P<0.05), while hippocampal levels of GSK-3 in intervened groups were lower (P<0.01).</p><p><b>CONCLUSION</b>HNYC extract could obviously increase the protein expressions of PKC and TrkA and decrease the expression of GSK-3 protein in brain tissue of transgenetic mice model of dementia, and regulate APP metabolic signal transduction path, and thus to suppress the production of Aβ, which is one of the dominant mechanisms for improving learning/memory capacity of dementia model animals.</p>

Effect of early intervention with extract of Huannao Yicong Decoction (还脑益聪方) on the pathologic picture of hippocampus and neurocyte apoptosis in APP transgenic mice model of dementia / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of early intervention using extract of Huannao Yicong Decoction (, HYD) on the pathological picture of hippocampus, neurocyte apoptosis, and associated regulatory genes in β-amyloid precursor protein (APP) transgenic mice model of dementia.</p><p><b>METHODS</b>Sixty APP695(V7171) transgenic mice were randomly divided into four groups of 15. The model group was treated with distilled water, the positive control group was treated with donepezil (0.65 mg/kg), and the two HYD groups were treated with high dose (2.8 g/kg) and low dose (1.4 g/kg) HYD, respectively. All testing drugs were administered through gastrogavage by dissolving in equal volume of distilled water, once a day for six successive months. In addition, a normal control group with 15 healthy C57BL/6J mice of the same age and genetic background was set up with distilled water treatment. The pathologic picture of brain tissue was observed by microscopy with HE stain; the amount of apoptosis cells in the hippocampal CA1 area was detected by TUNEL; and expressions of associated genes, Bcl-2, and Bax were determined by immunohistochemical method.</p><p><b>RESULTS</b>Pathologic pictures of hippocampus showed that in the model group, cells messily arranged, neurons markedly decreased, and the surrounding tissue of some cells was loosened with edema, necrosis, and widened gap with glia cells proliferation. Compared with those in the normal group, the amount of apoptosis cells in the CA1 area was increased, Bcl-2 expression decreased, and Bax expression increased significantly, with markedly reduced Bcl-2/Bax ratio in the model group. Compared to the model group, the pathological changes were significantly milder in the HYD-treated groups, showing rather regularly arranged cells, significantly increased neurons, only few denatured necrotic cells with milder edema, less proliferation of glia cells, and obviously reduced cell apoptosis in CA1 area (P<0.05 or P<0.01). Besides, Bcl-2 expression was up-regulated and Bax expression down-regulated, and Bcl-2/Bax ratio significantly increased in the two HYD groups (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Early intervention with HYD could improve the abnormal pathologic picture of hippocampus and regulate the expressions of associated genes to suppress cell apoptosis, which might be its mechanism of action in alleviating cognitive functional disorder.</p>

Effect of traditional and integrative regimens on quality of life and early renal impairment in elderly patients with isolated systolic hypertension / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of Chinese medical regimen and integrative medical regimen on quality of life and early renal impairment in elderly patients with isolated systolic hypertension (EISH).</p><p><b>METHODS</b>A multi-center, randomized, double-blinded controlled trail was adopted. A total of 270 cases of EISH were randomly divided into 3 groups: Chinese medicine group (CM), combination group and Western medicine group (WM). The course of treatment was 4 weeks. The clinical blood pressure, integral of quality of life (SF-36 scale), immunoglubin G (IgG), microalbumin (mALB), beta(2)-microglobulin (beta(2)-MG), transferrin (TRF) and N-acetyl-beta'-D-glucosa-minidase (NAG) in urine were determined before and after the treatment.</p><p><b>RESULTS</b>After treatment, systolic blood pressure depressed significantly in each group (P<0.05), and the combination group was superior to CM or WM group in depressing SBP (P<0.05); in each group, integral of quality of life improved in different degree, and combination group was superior to WM group in all 8 dimensions (P<0.05). The level of mALB and beta(2)-MG in urine decreased in all groups (P<0.05), and the combination group was superior to CM group or WM group in decreasing mALB (P<0.05).</p><p><b>CONCLUSIONS</b>Chinese medical regimen has affirmative effect in treating EISH patients, and could lower the systolic blood pressure, improve quality of life and early renal impairment of the patients, and integrative medical regimen has superiority on account of cooperation, and deserves further study.</p>