Wogonoside alleviates high glucose-induced dysfunction of retinal microvascular endothelial cells and diabetic retinopathy in rats by up-regulating SIRT1 / 南方医科大学学报

OBJECTIVE@#To investigate the effects of wogonoside on high glucose-induced dysfunction of human retinal microvascular endothelial cells (hRMECs) and streptozotocin (STZ)-induced diabetic retinopathy in rats and explore the underlying molecular mechanism.@*METHODS@#HRMECs in routine culture were treated with 25 mmol/L mannitol or exposed to high glucose (30 mmol/L glucose) and treatment with 10, 20, 30, 40 μmol/L wogonoside. CCK-8 assay and Transwell assay were used to examine cell proliferation and migration, and the changes in tube formation and monolayer cell membrane permeability were tested. ROS, NO and GSH-ST kits were used to evaluate oxidative stress levels in the cells. The expressions of IL-1β and IL-6 in the cells were examined with qRT-PCR and ELISA, and the protein expressions of VEGF, HIF-1α and SIRT1 were detected using Western blotting. We also tested the effect of wogonoside on retinal injury and expressions of HIF-1α, ROS, VEGF, TNF-α, IL-1β, IL-6 and SIRT1 proteins in rat models of STZ-induced diabetic retinopathy.@*RESULTS@#High glucose exposure caused abnormal proliferation and migration, promoted angiogenesis, increased membrane permeability (P < 0.05), and induced inflammation and oxidative stress in hRMECs (P < 0.05). Wogonoside treatment concentration-dependently inhibited high glucose-induced changes in hRMECs. High glucose exposure significantly lowered the expression of SIRT1 in hRMECs, which was partially reversed by wogonoside (30 μmol/L) treatment; interference of SIRT1 obviously attenuated the inhibitory effects of wogonoside against high glucose-induced changes in proliferation, migration, angiogenesis, membrane permeability, inflammation and oxidative stress in hRMECs. In rat models of STZ-induced diabetic retinopathy, wogonoside effectively suppressed retinal thickening (P < 0.05), alleviated STZ-induced retinal injury, and increased the expression of SIRT1 in the retinal tissues (P < 0.001).@*CONCLUSION@#Wogonoside alleviates retinal damage caused by diabetic retinopathy by up-regulating SIRT1 expression.

Effects ofGly14-Humanin on oxidative stress and neuron apoptosis in rats after focal cerebral ischemia reperfusion injury / 预防医学

Objective To study the effect of [Gly14]-Humanin on oxidative stress and neuron apoptosis after focal cerebral ischemia reperfusion injury in rats. Methods A rat model of acute middle cerebral artery occlusion(MCAO)and reperfusion was established by suture embolism. Ninety-six healthy male Sprague-Dawley rats were randomly divided into sham-operation group, model group, normal saline group and HNG group. And 5 μL HNG(100 nmol/L)in the rats of the HNG group, normal saline in the rats of the sham-operation group and normal saline group were given to rats 3 days before operation respectively(iv, three times, qd). After cerebral ischemia 3 h and 24 h of reperfusion, neurological deficit score(NDS) were performed for each group, and the activity of sod, levels of GSH and MDA in cerebral tissue were detected. TUNEL staining were used to detect neuronal apoptosis. Results Median(Interquartile range)of NDS was 0(0)in sham-operation group, 1.5(1)in model group, 3(1)in normal saline group and 3(1)in HNG group, respectively, and the NDS of sham-operation group was significantly lower than the other three groups. The NDS of HNG group was significantly lower than the model group and normal saline group(all P<0.05). Compared with sham-operation group, the activity of SOD of model group, normal saline group and HNG group rats[(11.65±1.66),(12.15±1.56)and (19.43±1.47)U/mL]and levels of GSH[(8.84±1.23),(7.51±1.16)and (11.17±1.67)mg/L]were decreased, and levels of MDA[(42.61±1.79), (40.33±1.24)and (35.39±1.29)nmol/mL]were increased(P<0.05). The activity of SOD and levels of GSH of HNG group were significantly higher than model group and normal saline group, but the levels of MDA was significantly lower than model group and normal saline group(all P<0.05). Compared with sham-operation group[(0.13±0.01)%], percentage of neuronal apoptosis of model group, normal saline group and HNG group rats[(0.59 ±0.07)%,(0.51 ±0.08)% and (0.22 ±0.03)%, respectively]were increased(P<0.05), and percentage of neuronal apoptosis of HNG group was significantly lower than model group and normal saline group(all P<0.05). Conclusion By increasing the activity of SOD and levels of GSH,[Gly14]-Humanin can resist focal cerebral ischemia reperfusion injury, and can decrease the neuro apoptosis of ischemic area, thus mitigate the neurologic deficit.

Clinical application of proton magnetic resonance spectroscopy in children with idiopathic epilepsy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>This study examined the biochemical metabolism by proton magnetic resonance spectroscopy ('H-MRS) in order to explore the value of 'H-MRS in idiopathic epilepsy in children.</p><p><b>METHODS</b>Thirty-three children with idiopathic epilepsy (14 cases with history of febrile seizures and 19 cases without) and six normal controls experienced MRI of the skull and brain and single-voxel 'H-MRS examinations of the hippocampi-temporal lobe. The signal intensities of N-acetylaspartate (NAA), eatine+phosphocreatine (Cr), choline-containing compounds (Cho) and lactate (Lac) and the ratios of NAA/ (Cho+Cr) and Lac/Cr were compared between the patients and normal controls.</p><p><b>RESULTS</b>MRI examination showed that only one child with epilepsy had myelin dysplasia. 'H-MRS examination showed that the ratio of NAA/ (Cho+Cr) in the epilepsy group was lower than that in the control group (0.64+/-0.07 vs 0.73+/-0.05; P<0.01). The epileptic children with history of febrile seizures had a more decreased ratio of NAA/ (Cho+Cr) compared with those without the history (0.61+/-0.07 vs 0.66+/-0.06; P<0.05). There were no significant differences in the ratio of Lac/Cr between the epilepsy and the control groups.</p><p><b>CONCLUSIONS</b>'H-MRS may provide early information on brain injury sensitively and non-invasively in children with epilepsy. It may be used for diagnosis and prognosis evaluation of epilepsy.</p>

The expression of hepatitis B virus X protein and cyclooxygenase-2 in hepatitis B virus-related hepatocellular carcinoma: correlation with microangiogenesis and metastasis, and what is the possible mechanism / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the expression of HBx and COX-2 in hepatitis B virus-related hepatocellular carcinoma, and Its correlation with microangiogenesis and metastasis, and possible mechanism.</p><p><b>METHODS</b>Immunohistochemistry was used to detect the expression of hepatitis B virus X, cyclooxygenase-2 and CD34 in hepatitis B virus related hepatic carcinoma and 22 non-HBV related hepatic carcinoma tissues. The expression of hepatitis B virus x protein and cyclooxygenase-2 in hepatitis B virus-related hepatocellular carcinoma correlated with microangiogenesis and metastasis was tested by Spearman correlation analysis. The expression of COX-2 in HepG2-X was detected by Western blot and RT-PCR. PGE2 was detected by ELISA in clear supernatant liquid of HepG2-X. Trypan blue exclusion was performed to examine the inhibitory effects of COX-2 selective inhibitor (celecoxib).</p><p><b>RESULTS</b>In Hepatitis B carcinoma tissue, HBx and COX-2 were expressed at high level. The positive rate of COX-2 expression was 88.87% (55/62) in HBx positive expression group, which was significantly higher than that of the positive expression 31.82% (7/22, x2=27.188, P<0.01) in HBx negative expression group and 40.91% (9/22, x2=20.453, P<0.01) in non-HBV related hepatic carcinoma tissues, but it had no statistical difference (x2=0.393, P=0.531) between the HBx negative expression group and non-HBV related hepatic carcinoma tissue group. The expressions of HBx and COX-2 in metastasis group were higher than that in non-metastasis group (P<0.01), MVD in HBx or COX-2 positive expression group was significantly higher than that in negative expression group and non-HBV related hepatic carcinoma tissues (P is less than 0.01). MVD with metastasis was higher than that without metastasis (P<0.01) and MVD with portal vein invasion was higher than that without invasion (P<0.05). Spearman correlation analysis showed that the expression of COX-2 was significantly correlated with the expression of HBx (Rs=0.568, P<0.01). Celecoxib suppressed the growth of both cells in a dose-dependent manner. HepG2-X was significantly susceptible to celecoxib as compared to the HepG2-PC cells. COX-2 protein and mRNA were upregulated in HepG2-X cells than in HepG2-PC. Moreover, PGE2 was upregulated in clear supernatant liquid of HepG2-X than in HepG2-PC.</p><p><b>CONCLUSION</b>The expressions of HBx and COX-2 were higher in HBV-related hepatocellular carcinoma. COX-2 was significantly correlated with HBx in HCC and it could be a key factor involved in HBx contributed hepatocellular carcinoma's microangiogenesis and metastasis. The possible mechanism of the dual effects might be through HBx, COX-2 and PGE2 pathways in infiltration involved metastasis and microangiogenesis involved metastasis.</p>

Effect of histamine H4 receptor and its antagonist on allergic rhinitis in rats / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To clarify the effect of histamine H4 receptor antagonist, JNJ 7777120, and histamine H1 receptor antagonist, Loratadine, on allergic rhinitis (AR) in rats and to study the role of histamine H4 receptor antagonist and histamine H1 receptor antagonist in the pathogenesis of allergic rhinitis and therapeutic value of their antagonist.</p><p><b>METHODS</b>AR animal model were induced by ovalbumin (OVA) in the Wistar rats, which treated with histamine H4 receptor antagonist and (or) histamine H1 receptor antagonist. The allergic symptoms (sneezing and nasal rubbing), serum total IgE and the levels of cytokines in serum or nasal lavage fluid were measured, the diversity between two groups were observed. Statistical analysis was performed using a SPSS 13.0 software.</p><p><b>RESULTS</b>Compared with AR group with no treatment, the inhibition of nasal symptoms (P < 0.01), a significant decrease in the levels of IgE, IL-4 in serum and Eotaxin in nasal lavage fluid (P < 0.01), a significant increase in the levels of IFN-γ in serum (P < 0.01) after treatment was found. Compared with group treated with Loratadine, inhibition of nasal symptoms (q value were 3.72, 4.16, P < 0.01), a significant increase in the levels of IgE and IL-4 in serum (q value were 8.01, 4.96, P < 0.05), a significant decrease in the levels of IFN-γ in serum (q = 3.18, P < 0.05) in group treated with JNJ 7777120 also, but no significant differences in the levels of Eotaxin in nasal lavage fluid (P > 0.05). Administration of JNJ 7777120 and Loratadine jointly, neither additive effect nor synergistic action were found (P > 0.05).</p><p><b>CONCLUSIONS</b>Histamine H4 receptor is closely related with allergic rhinitis and is important in the pathogenesis of allergic rhinitis, the same as histamine H1 receptor. Histamine H4 receptor antagonist, JNJ 7777120, could relieve symptoms and inflammatory conditions in allergic rhinitis, the effect was weak compared with Loratadine. Neither additive effect nor synergistic action were found between them.</p>