Effect of Methyl-CpG binding domain protein 2 (MBD2) on AMD-like lesions in ApoE-deficient mice / 华中科技大学学报（医学）（英德文版）

The role of methyl-CpG binding domain protein 2 (MBD2) in an ApoE-deficient mouse model of age-related macular degeneration (AMD) was investigated. Eight-week-old Mbd2/ApoE double deficient (Mbd2(-/-) ApoE(-/-)) mice (n=12, 24 eyes, experimental group) and MBD2 (wt) ApoE(-/-) mice (n=12, 24 eyes, control group) were fed on Western-type diet for 4 months. The mice were sacrificed, and total serum cholesterol levels were analyzed and Bruch's membrane (BM) of the eyes was removed for ultrastructural observation by transmission electron microscopy. Moreover, intercellular adhesion molecule 1 (ICAM-1) immunoreactivities were evaluated by fluorescence microscopy in sections of the eyes in both groups for further understanding the function mechanism of MBD2. There was no significant difference in the total serum cholesterol levels between control group and experimental group (P>0.05). Transmission electron microscopy revealed that AMD-like lesions, various vacuoles accumulated on BM, notable outer collagenous layer deposits and dilated basal infoldings of retinal pigment epithelium (RPE) were seen in both groups, and the BM in control group was significantly thickened as compared with experimental group (P<0.05). Fluorescence micrographs exhibited the expression of ICAM-1 in choroid was higher in control group than in experimental group. We are led to conclude that MBD2 gene knockout may lead to accumulation of more deposits on the BM and influence the pathogenesis of AMD via triggering endothelial activation and inflammatory response in choroid, improving microcirculation, and reducing lipid deposition so as to inhibit the development of AMD-like lesions. Our study helps to provide a new therapeutic approach for the clinical treatment of AMD.

Effect of Methyl-CpG binding domain protein 2 (MBD2) on AMD-like lesions in ApoE-deficient mice / 华中科技大学学报（医学）（英德文版）

The role of methyl-CpG binding domain protein 2 (MBD2) in an ApoE-deficient mouse model of age-related macular degeneration (AMD) was investigated. Eight-week-old Mbd2/ApoE double deficient (Mbd2(-/-) ApoE(-/-)) mice (n=12, 24 eyes, experimental group) and MBD2 (wt) ApoE(-/-) mice (n=12, 24 eyes, control group) were fed on Western-type diet for 4 months. The mice were sacrificed, and total serum cholesterol levels were analyzed and Bruch's membrane (BM) of the eyes was removed for ultrastructural observation by transmission electron microscopy. Moreover, intercellular adhesion molecule 1 (ICAM-1) immunoreactivities were evaluated by fluorescence microscopy in sections of the eyes in both groups for further understanding the function mechanism of MBD2. There was no significant difference in the total serum cholesterol levels between control group and experimental group (P>0.05). Transmission electron microscopy revealed that AMD-like lesions, various vacuoles accumulated on BM, notable outer collagenous layer deposits and dilated basal infoldings of retinal pigment epithelium (RPE) were seen in both groups, and the BM in control group was significantly thickened as compared with experimental group (P<0.05). Fluorescence micrographs exhibited the expression of ICAM-1 in choroid was higher in control group than in experimental group. We are led to conclude that MBD2 gene knockout may lead to accumulation of more deposits on the BM and influence the pathogenesis of AMD via triggering endothelial activation and inflammatory response in choroid, improving microcirculation, and reducing lipid deposition so as to inhibit the development of AMD-like lesions. Our study helps to provide a new therapeutic approach for the clinical treatment of AMD.

Effects of perfluorooctane sulfonate on learning and memory of rat pups / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the effects of prenatal and postnatal perfluorooctane sulfonate (PFOS) exposure on spatial learning and memory, N-methyl-D-aspartate receptor 2B (NR2B) mRNA and protein level in frontal cortex and hippocampus of rat pups and to explore the mechanism of developmental neurotoxicity induced by PFOS.</p><p><b>METHODS</b>Twenty-eight pregnant rats were randomly divided into three groups in proportion of 3:2:2, including control group (C), low dose group (L) and high dose group (H) by means of randomized number table, which respectively received 0, 7.2, 14.4 mg/kg PFOS feed from pregnancy day 0 to postnatal day (PND) 30 by free feedings. The animal models of prenatal and postnatal non-exposure (CC), prenatal exposure (LC and HC), postnatal exposure (CL and CH), and prenatal and postnatal exposure (LL and HH) to PFOS were established by cross-fostering method. The spatial learning and memory were measured by water maze experiment,the NR2B mRNA levels in frontal cortex of rat pups was determined with semi-quantitative RT-PCR, NR2B protein express in cerebral cortex (frontal and temporal cortex) and hippocampus (CA1, CA3, CA4 and DG regions) of rat pups was detected by immunohistochemistry.</p><p><b>RESULTS</b>The escape latency of CL, CH, LL and HH groups pups in water maze experiment were (99.83 +/- 25.77) s, (111.30 +/- 17.82) s, (106.40 +/- 18.71) s, (107.70 +/- 16.85) s, and longer as compared with CC group [(54.90 +/- 26.69) s] (q value were 4.349, 4.773, 6.026 and 5.641, respectively, P <0.01). The number of errors of HH group rat pups entering dead end was (22.30 +/- 7.56) at the training day 4, and it was significantly higher than that of CC group (9.80 +/- 4.64) (q = 5.173, P < 0.01). The NR2B mRNA levels of frontal cortex of pups in HC group at PND1, and LC group, HC group and HH group at PND14 were (0.167 +/- 0.008), (0.364 +/- 0.035), (0.341 +/- 0.030) and (0.328 +/- 0.045) respectively,which were significantly lower than CC group (0.271 +/- 0.060) and (0.465 +/- 0.067) (q values were 3.547, 3.739, 4.597 and 5.006, respectively, P< 0.05 ). The results of immunohistochemistry indicated that NR2B protein express of the hippocampus CA1 region of pups in LC group was (0.091 +/- 0.005), and showed significant lower than CC group which was (0.123 +/- 0.009) at PND1 (q = 5.209, P <0.05). At PND14, the effect of PFOS extended to cerebral cortex and hippocampus regions. At PND28, the effects of PFOS were showed in hippocampus CA1, CA3 and temporal cortex regions.</p><p><b>CONCLUSION</b>Prenatal and postnatal exposure to PFOS should result in the spatial learning and memory damage,and the mechanism might be possibly involved in the decrease of NR2B level in cerebral cortex and hippocampal formation regions.</p>

Comparative study on the acute toxicity of pulmonary caused by nanosized and microsized powders of silicon dioxide / 中华预防医学杂志

<p><b>OBJECTIVE</b>To compare the acute pulmonary toxicities of nanosized and microsized silicon dioxide particles.</p><p><b>METHODS</b>All 125 healthy male Wistar rats were divided into 25 groups randomly according to the weight. Experimental animals were exposed to microsized SiO2 at the doses of 100 mg/m3 (group A) and 300 mg/m3 (group B), and to the nanosized SiO2 at the same dose levels (group A' and B') by inhalation for 2 hours. Compositions in bronchoalveolar lavage fluids (BALF) and contents of hydroxyproline in blood sera and lung tissues were detected and then compared at 6, 12, 24, 48, 72 hours after administration.</p><p><b>RESULTS</b>The total cellular score (TCS) in BALF of group A'[(55.00 +/- 8.30) x 10(4)/ ml] and B'[(52.50 +/- 9.02) x 10(4)/ml] at 6 hours were significantly higher than those in control groups [(34.88 +/- 12.53) x 10(4)/ml]; TCS in BALF of group A' [(55.00 +/- 8.30) x 10(4)/ml]at 6 hours and group A' [(39.75 +/- 12.08) x 10(4)/ml] at 24 hours were significantly higher than those in isodose group of microsized SiO2 [(32.38 +/- 13.07) x 10(4)/ml, (24.13 +/- 10.97) x 10(4)/ml) ]; total protein (TPr) in BALF of group A' [(0.34 +/- 0.09)g/L] and B' [(0.38 +/- 0.16) g/L] at 48 hours were significantly higher than those in isodose group of microsized SiO2 [(0.20 +/- 0.07) g/L, (0.21 +/- 0.05) g/L]. Lactate dehydrogenase (LDH) in BALF of group A' [(1.66 +/- 0.22) x 10(3) U/L] at 72 hours were significantly higher than those in isodose group of microsized SiO2 [(1.38 +/- 0.17) x 10(3) U/L]. Alkaline phosphatase (AKP) in BALF of group B' [(5.14 +/- 1.47) U/100 ml] at 6 hours and group B' [(5.86 +/- 2.41) U/100 ml] at 24 hours were significantly higher than those in isodose group of microsized SiO2 [(3.64 +/- 0.36) U/100 ml, (3.30 +/- 2.19) U/100 ml]. Hydroxyproline (HyP) in tissues of lung of group A' [(0.532 +/- 0.053) microg/mg, (0.484 +/- 0.046) microg/mg, (0.591 +/- 0.096) microg/mg, (0.551 +/- 0.084) microg/mg] at 6, 12, 48, 72 hours and group B' [(0.508 +/- 0.081) microg/mg, (0.565 +/- 0.053) microg/mg ] at 12, 72 hours were significantly higher than those in isodose group of microsized SiO2 [(0.345 +/- 0.074) microg/mg, (0.368 +/- 0.095) microg/mg, (0.431 +/- 0.036) microg/mg, (0.399 +/- 0.080) microg/mg, (0.396 +/- 0.039) microg/mg, (0.465 +/- 0.062) microg/mg].</p><p><b>CONCLUSION</b>Nanosized and microsized SiO2 should have some differences on acute pulmonary toxicities in our experiment condition.</p>

Effects of perfluorooctane sulfonate on Glu, PKC and PKA activities in mouse brain / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the effects of perfluorooctane sulfonate (PFOS) on contents of glutamate and activity of protein kinase C (PKC) and A (PKA) and ultrastructure injury in the brain of male mice and to explore the mechanism of neurotoxicity and patho-alteration resulted from PFOS.</p><p><b>METHODS</b>44 male mice were randomly divided into four groups, who were respectively orally given 0, 5, 10, 20 mg/kg PFOS for 10 days. The Glu consents in the brain of the mice was measured with spectrophotometer and protein kinases activity were measured with non-radioactive assay of protein kinase and the changes of cerebral cortex ultrastructure were observed.</p><p><b>RESULTS</b>Contents of Glu in 10 and 20 mg/kg groups were (1.57 +/- 0.11) and (1.62 +/- 0.16) mmol/g prot respectively,which was significantly increased compared with the corresponding controlled group [(1.45 +/- 0.13) mmol/g prot] (F = 39.59, P < 0.05). PKC activity in 5, 10 and 20 mg/kg BW groups were (29.05 +/- 2.89), (33.65 +/- 3.82) and (34.20 +/- 3.16) pmol x min(-1) x (mg prot)-1 respectively, which was significantly increased compared with the corresponding control group [(24.53 +/- 2.88) pmol x min(-1) x (mg prot)-1] (F = 7.75, P < 0.05). Compared with the corresponding control group, PKA in 5, 10 and 20 mg/kg BW groups increased by (24.12 +/- 3.86)%, (34.02 +/- 3.04)% and (33.42 +/- 3.71)% with a statistical significance (F = 26.27, P < 0.01). The exposed mice had cerebral cortex ultrastructure injury of cell nucleus envelope hollow.</p><p><b>CONCLUSION</b>Exposure to PFOS increases Glu contents and activity of PKC and PKA in mouse brain and induce the cerebral cortex ultrastructural injury, a possible mechanism of the neurotoxicity caused by PFOS.</p>