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OBJECTIVE@#To investigate the ameliorate effect and underlying mechanism of Xueshuantong for Injection (Lyophilized, , XST) in streptozocin (STZ)-induced diabetic retinopathy (DR) rats.@*METHODS@#Diabetes mellitus (DM) model was induced by intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Diabetic rats were randomized into 3 groups (n=10) according to a random number table, including DM, XST50 and XST100 groups. XST treatment groups were daily i.p. injected with 50 or 100 mg/kg XST for 60 days, respectively. The control and DM groups were given i.p. injection with saline. Blood glucose level and body weight were recorded every week. Histological changes in the retina tissues were observed with hematoxylin-eosin staining. Apoptosis and inflammation related factors, including cleaved caspase-3, glial fifibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α) and intercellular cell adhesion molecule-1 (ICAM-1) were detected by Western blot or real-time polymerase chain reaction. Then, the levels of advanced glycation end product (AGE) and its receptor (RAGE) were investigated. Tight junctions proteins (Zonula occludens-1 (ZO-1), Occludin and Claudin-5) of blood-retinal barrier were detected by Western blot. The levels of retinal fifibrosis, transforming growth factor-β1 (TGF-β1)-Smad2/3 signaling pathway were evaluated at last.@*RESULTS@#There was no signifificant difference in the body weight and blood glucose level between XST and DM groups (P>0.05). Compared with the DM group, XST treatment signifificantly increased the retinal thickness of rats (P<0.05 or P<0.01), and suppressed cleaved caspase-3 expression (P<0.01). XST increased the protein expressions of ZO-1, Occludin and Claudin-5 and decreased the mRNA expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 (P<0.05 or P<0.01). Moreover, XST signifificantly reduced the productions of AGE and RAGE proteins in the retina of rats (P<0.05 or P<0.01), suppressed the over-expression of TNF-α, and decreased the elevated level of ICAM-1 in retina of rats (P<0.05 or P<0.01). XST signifificantly reduced the levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), TGF-β1 and phosphorylation of Smad2/3 protein in rats (P<0.05 or P<0.01).@*CONCLUSIONS@#XST had protective effects on DR with possible mechanisms of inhibiting the inflammation and apoptosis, up-regulating the expression of tight junction proteins, suppressing the productions of AGE and RAGE proteins, and blocking the TGF-β/Smad2/3 signaling pathway. XST treatment might play a role for the future therapeutic strategy against DR.
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Objective To investigate the intelligence standard for diagnose the sub-cretin children and children with mental retardation of socio-cultural type.Methods The full intelligence quotient(IQ),verbal intelligence quotient(VIQ)and performance intelligence quotient(PIQ)was tested by Wechsler scale(C-WISC)for mild iodine deficiency disordem children,children living in abnormal socio-cultural condition and normal children aged 7～14 years old in Qinba mountain area.The test results had been compared between the groups.Results There were no significant difference between psychomotor functioning well children and children living normal sociocuhural condition in VIQ,PIQ and full IQ(89.24±18.44 vs 90.75±17.58,87.58±15.78 vs 88.95±15.56,87.42±17.84 vs 89.02±17.18,t=1.14,1.19 and 1.24,respectively,all P＞O.05).PIQ and full IQ were significantly lower in mild iodine deficiency disorders children than in children with abnormal socio-cultural background (65.81±10.22 vs 72.33±13.23,62.42±12.31 vs 68.13±14.54,t=3.26,2.55,P＜0.01 or＜0.05,respectively).But the VIQ was not significantly different between these two groups.The average difference of VIQ and PIQ among mild iodine deficiency disorders children wag-0.32 without significant difierence(t=0.28,P＞0.05),however it was-2.91 among children under abnormal socio-cultural condition with significant difierenee(t=-3.59,P＜0.01).Conclusions IQ for iodine deficiency disorders children is characterized by that VIQ is damaged in parallel with PIQ,while that in children under abnormal soeio-cuhural condition is marked by that VIQ is retarded more severely than PIQ,which ean be used as an intelligence standard for differentiating the sub-cretin children from children wjth socio-cuhural mental retardation.
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<p><b>OBJECTIVE</b>Fructose-1, 6-diphosphate (FDP), serving as a cellular energy substance, has shown its roles in the treatment of hypoxic-ischemic encephalopathy and myocardial damage. The present study aimed at exploring the potentiality of the protective effect of FDP against ultrastructural damage of the hippocampus caused by febrile seizures (FS) in rats.</p><p><b>METHODS</b>Thirty-six 21-day-old male Sprague-Dawley rats were randomly divided into three groups: untreated FS (control), high-dose FDP-treated FS and low-dose FDP-treated FS. FS were induced by hyperthermal bath. Thirty minutes before FS induction, rats in the high-dose and low-dose FDP-treated groups received a peritoneal injection of FDP at a dosage of 50 and 25 mg per 100 g of body weight respectively, whereas the same volume of 0.9% sodium chloride solution were injected to the rats in the control group. Transmission electron microscopy was used to examine the ultrastructural pathologic changes of neurons and organelles as well as the features of synaptic morphological parameters in the hippocampal CA1 area.</p><p><b>RESULTS</b>Neuronal degeneration and necrosis, mitochondria swelling, polyribosomes disaggregation from endoplasmic reticula, and golgiosomes dilation in the hippocampal CA1 area in the two FDP intervention groups were less severe compared with the control group. FDP treatment resulted in significant increases in postsynaptic density thickness (F=12.47, P<0.01), synaptic active zone length (F=14.75, P<0.01) and synaptic interface curvature (F=3.77, P<0.05), as well as a shorter interspace of neural synapses (F=7.29, P<0.01) when compared with the control group. There were no significant differences in the ultrastructural changes between the two FDP treatment groups.</p><p><b>CONCLUSIONS</b>FDP can ameliorate ultrastructural damage in the hippocampus caused by FS in rats. However, further research is warranted for a reasonable and effective dosage of FDP.</p>
Subject(s)
Animals , Male , Rats , Fructosediphosphates , Therapeutic Uses , Hippocampus , Neuroprotective Agents , Therapeutic Uses , Rats, Sprague-Dawley , Seizures, Febrile , Drug Therapy , PathologyABSTRACT
<p><b>OBJECTIVE</b>Febrile seizure is a very common emergency in children. Although researchers home and abroad constantly pay close attention to studies on brain damage and lesion possibly caused by febrile seizure, studies of effects on motor, behavior, spatial learning and memory are relatively seldom. In our study, Sprague-Dawley rats were utilized for the purpose of the exploration of effects of febrile seizures on their motor, behavior, spatial learning and memory.</p><p><b>METHODS</b>Sixty 21-day-old male Sprague-Dawley rats, weighing (50 +/- 5) g were divided randomly and equally into febrile seizure group (FS), febrile control group (FG) and normal control group (NG). Febrile seizure animal model was induced by hyperthermal bath with 45 degrees C water. Febrile seizure was induced twice a day, thus ten times within five days in FS group. Rats of FG group were immersed in the same hyperthermal water for 2 minutes. Nothing special was performed on NG group. The abilities of motor and behavior of every rat in these 3 groups were tested in inclined plane test (IPT), overhanging test (OHT) and open field test (OFT) to show their varieties. Furthermore, Morris water maze was applied to evaluate the effects by febrile seizure on spatial learning and memory in rats during the place navigation test and spatial probe test.</p><p><b>RESULTS</b>In the present experiments, febrile seizures were altogether induced 192 times with the mean latency being (4.25 +/- 0.98) minutes and the mean duration being (1.06 +/- 0.59) minutes. The experiments confirmed that multiple febrile seizures could lead to decreases of abilities in all tests in which analysis of variance indicated that there were significant differences between febrile seizure group and the other two (P < 0.01). In inclined plane test, the turning ability of the rats was weakened. The mean turning time was (9.1 +/- 2.6) seconds for FS, (5.3 +/- 2.1) seconds for FG and (5.3 +/- 2.0) seconds for NG. In overhanging test, the overhanging time was shortened: (33.4 +/- 18.1) seconds for FS, (50.1 +/- 20.3) seconds for FG and (59.0 +/- 20.7) seconds for NG. In the open field test, the rats became less active with the scores (5.1 +/- 2.0) for FS, (10.4 +/- 3.0) for FG and (13.2 +/- 2.3) for NG. Meanwhile, the authors discovered the decreases of the abilities of spatial learning and memory in rats caused by febrile seizures many times. In the place navigation test, the mean escape latency for the rats' looking for hidden platform was prolonged; the efficiency of their search strategy decreased; the swimming time the animals spent in platform region decreased [(44.02 +/- 5.25) seconds for FS, (51.75 +/- 5.28) seconds for FG and (57.07 +/- 5.36) seconds for NG; analysis of variance, P < 0.01.]; the number of times they crossed the platform area decreased [(6.07 +/- 1.77) times for FS, (9.25 +/- 2.07) times for FG and (11.34 +/- 2.37) times for NG; analysis of variance, P < 0.01]; the percentage of their swimming time fell (36.68% for FS, 43.13% for FG and 47.56% for NG).</p><p><b>CONCLUSION</b>The experiments confirmed that multiple febrile seizures could result in damage and lesion of motor, behavior, spatial learning and memory in rats.</p>
Subject(s)
Animals , Male , Rats , Maze Learning , Physiology , Memory , Physiology , Motor Activity , Physiology , Random Allocation , Rats, Sprague-Dawley , Seizures, Febrile , Spatial Behavior , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>Febrile seizure (FS) is a pediatric emergency. The reiterative attacks of FS may result in brain damage to various extents. Fructose-1,6-diphosphate, serving as a cellular energy substance, has been applied to clinical practice for many years and has shown its importance in adjuvant treatment of diseases with myocardial damage. This study aimed to explore the potentiality of protecting rats' brain damage caused by febrile seizure with fructose-1,6-diphosphate (FDP).</p><p><b>METHODS</b>Thirty 21-day-old male Sprague-Dawley (SD) rats were randomly divided into febrile seizure group (FS), sodium chloride solution (NS) control group and FDP intervention group (FD). Febrile seizure was induced by hyperthermal bath at 45 degrees C in the present study. No intervention treatment was given to rats in FS group before febrile seizure. Thirty minutes before febrile seizures, rats in FD group were given peritoneal injection of FDP at a dose of 25 mg per 100 g of body weight, whereas the same volume of 0.9% sodium chloride solution was injected into peritoneum of rats in NS group. Manifestations of seizure and differences in seizure latency, duration of seizure and seizure severity were observed in all the 3 groups. Samples of rat brain were prepared for electron microscopy in order to understand the characteristics of the ultrastructural changes in mitochondria, interspace of neuronal synapses and neurons of hippocampal region CA(1).</p><p><b>RESULTS</b>Data collected from this study indicated that peritoneal injection of FDP at 25 mg per 100 grams of body weight 30 minutes before febrile seizures could result in improvement of the clinical manifestation of the rats caused by febrile seizures. Specifically speaking, the seizure latency was prolonged, the duration of seizures was shortened and severity of seizure was reduced. Analysis of variance and q-test on the data collected from the 3 groups revealed that there were significant differences between FD group and the other two groups (P < 0.05), yet no significant difference was found between FS group and NS group (P > 0.05). Electron microscopic observations on brain specimens revealed that FDP could relieve mitochondrial degeneration and edema. FDP could also reduce neuronal degeneration and necrosis in hippocampal region CA(1) (the percentages of neuronal degeneration and necrosis in the 3 groups were respectively 13% for FD group, 28% for FS group and 30% for NS group). There was a significant difference between FD group and the other two groups (P < 0.05), FDP treatment could prevent interspace of neuronal synapses from enlarging (the mean interspace was 6.47 +/- 0.37 micro m for FD group, 7.60 +/- 0.36 micro m for FS group and 7.53 +/- 0.40 micro m for NS group. The difference between FD group and the other two groups was significant (P < 0.01).</p><p><b>CONCLUSION</b>FDP could lead to prolonged seizure latency, shorter duration of seizures and mitigation of seizures severity. FDP could also reduce neuronal degeneration and necrosis and prevent the interspace of neuronal synapses from enlarging in hippocampal region CA(1). The present study suggests that FDP can protect brain of rat from damages caused by febrile seizures.</p>
Subject(s)
Animals , Male , Rats , Brain , Pathology , Disease Models, Animal , Fructosediphosphates , Therapeutic Uses , Neuroprotective Agents , Therapeutic Uses , Random Allocation , Rats, Sprague-Dawley , Seizures, Febrile , Drug Therapy , Treatment OutcomeABSTRACT
Objective To explore the expression of c-Fos protein and character of mossy fiber sprouting(MFS) in hippocampus of rat with febrile seizures(FS).Methods Thirty-six 21-day-old male Sprague-Dawley rats were randomly divided into FS group,febrile control(FG) group and normal control(NG) group.FS was established by hyperthermal bath.Immune histochemistry and(Timm′s) staining were used to examine the expression of c-Fos protein in CA1 region and MFS in CA3 region of hippocampus.Results Excessive expression of c-Fos protein presented in the hippocampal CA1 region of FS group.The surface area percentage of c-Fos protein of FS group[(2.26?0.23)%] was higher than that of FG group[(1.08?0.19)%] and NG group[(0.71?0.14)%],there were significant difference between FS group and the other two groups(?~2=10.48 P