Aging ; Animals ; Brain ; drug effects ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Male ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective To establish brain hypoxic-ischemic (HI) model using postnatal day 3(P3) SD rats and evaluate the apoptotic neuronal cells in cerebral cortex and neurofunctional development.Methods The P3 rats were randomly divided into HI group (n=35) and control group(n=18).HI was induced in P3 rats with right carotid artery ligation followed by 2.5 h hypoxia in 60 mL?L-1 oxygen at 37 ℃.The injury of neural cells in the cerebral cortex was evaluated by tumor necrosis factor receptor-1(TNF-R1),Caspase-3 immunostaining and Hematoxylin-Eosin (HE) staining in 24 h and 7 d after HI,respectively.Furthermore,the neurofunctional development was evaluated by negative geotaxis reflex and eye opening time.The data were analyzed by SPSS 12.0 software.Results Caspase-3 and TNF-R1 positive cells were abundant in the ipsilateral cortex at 24 h after HI,compared with contralateral part and control group(P

Objective To investigate the effects of interleukin?17A on kidney injury induced by paraquat(PQ). Methods Seventy?two ICR mice were randomly divided into 3 groups:NS,PQ,and PQ+Ab (n=24 for each). The PQ?poisoning model was established by administering a gavage of PQ solution;mice in the PQ+Ab group were then administereda dose of anti?IL?17A antibody 2 hours later by i.p. injection,whereas the NS group were administered a corresponding volume of normal saline instead.The mice were killed at 8,24,48,or 72 h to obtain renal tissues and serum. An enzyme?linked immunosorbent assay(ELISA)was used to determine serum IL?17A,serum creatinine(SCr),and blood urea nitrogen (BUN)levels.Chemical colorimetry was used to detect the viability of myeloperoxidase(MPO )in renal tissue,and hematoxylin?eosin(HE)stain?ing was used to observe the renal pathologic changes. Immunohistochemistry(IHC)and PCR were used to examine IL?17A expression in renal tis?sues. Results Serum IL?17A,renal tissue MPO viabilities,BUN,and SCr were increased in the PQ and PQ+Ab groups,compared to those in the NS group(P<0.01). However,the above?mentioned parameters were lower in the PQ+Ab group than in the PQ group(P<0.01). Conclusion IL?17A promotes mouse kidney injury induced by acute PQ?intoxication through activating and/or recruiting neutrophils;therefore,blockade IL?17A,with antibody can attenuate the injury.

Objective To investigate the role of interleukin-17A (IL-17A) in acute paraquat (PQ)-induced lung injury in mice.Methods A total of 120 healthy SPF grade ICR male mice were randomly (random number) divided into three groups (n =40 in each):normal saline control group (NS),PQ poisoning group (PQ) and antibody neutralization group (PQ + Ab).Mice of PQ group and PQ + Ab group were given 5 mg/mL PQ by one gavage in a dosage of 25 mg/kg body weight,and 5 μg IL-17A neutralizing antibody intra-peritoneally administered immediately after PQ poisoning in PQ + Ab group;Equivalent volume of normal saline instead of PQ was given to mice of NS group.Six survival mice from each group were taken for experiment at 8 h,1 d,3 d,5 d,7 d after PQ poisoning:Wet to dry ratio (W/D) of lung was determined in mice of each group.HE staining of lung tissue was used to observe the histopathological changes under the light microscope and the pathological scores were graded;Serum interleukin-17A (IL-17A),interleukin-22 (IL-22),interleukin-6 (IL-6),transforming growth factor-β (TGF-β) were detected with enzyme linked immunosorbent assay (ELISA);Expression of interleukin-23 receptor (IL-23R) in lung tissue was determined with immunohistochemical;real-time fluorescence quantification PCR (qRT-PCR) was used to detect the expression of retinoic acid related solitary nuclear receptors' mRNA in lung tissue.Results After administration of PQ,W/D ratio increased (P ＜ 0.01),lung injury was observed in mice of PQ and PQ + Ab groups,levels of cytokines (IL-17A,IL-22,IL-6 and TGF-β) in serum elevated (P ＜0.05),and the expressions of IL-23R mRNA and RORγt mRNA increased (P＜0.01).But in PQ +Ab group,W/D ratio decreased (P ＜0.05),lung injury was alleviated,the levels of cytokines (IL-17A,IL-22,IL-6 and TGF-β) decreased (P ＜ 0.05),and the expressions of IL-23R mRNA and RORγt mRNA reduced (P ＜ 0.05).Conclusions Since IL-17A involves in the lung injury of the mice induced by acute paraquat poisoning,blockade of IL-17A significantly alleviates the acute lung injury in mice.

Objective:To investigate the effect of electroacupuncture (EA) at Ganshu (BL 18) and Shenshu (BL 23) on vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1)/CD31 around the cerebral infarction focus in middle cerebral artery occlusion (MCAO) rats and the possible mechanism, thus to provide a new strategy for the treatment of cerebral ischemic stroke by acupuncture. Methods:A total of 180 healthy male Sprague-Dawley (SD) rats were randomly divided into a sham operation group, a model group, an acupoint group and a non-acupoint group, 45 rats in each group. MCAO model was established using the modified line-embolus method in all rats except for those in the sham operation group; rats in the acupoint group were treated with EA at Ganshu (BL 18) and Shenshu (BL 23); rats in the non-acupoint group were treated with EA at the control points; rats in other 2 groups were only subjected to bundling without treatment. Ten rats in each group were randomly selected on the 3rd day, the 14th day and the 21st day after acupuncture stimulation to test the neurological function impairment. The expression levels of CD31 and VEGF were also detected. Results:Compared with the model group and non-acupoint group, the neurological function score of the acupoint group was decreased at each time point, and the differences were statistically significant (P<0.05,P<0.01). The expressions of VEGF and CD31 in each group were the lowest on the 3rd day, reached the peak on the 14th day and still remained at high level on the 21st day. And the differences among groups were statistically significant both on the 14th day and the 21st day (P<0.05,P<0.01). Compared with the model group and the non-acupoint group, the expressions of VEGF and CD31 in the acupoint group were increased, and the differences were statistically significant (allP<0.05). Conclusion: EA at Ganshu (BL 18) and Shenshu (BL 23) can significantly improve the neurological function score of MCAO model rats, and shows protective effect on cerebral ischemia. The protective mechanism may be related to the up-regulation of CD31 and VEGF expression around the cerebral infarction focus in the MCAO model rats and induction of angiogenesis.

ObjectiveTocomparethedifferencesoftwostocksofguineapigs,thealbinoguineapigsandpigment guinea pigs , in establishing dyslipidemic model , to evaluate their lipid-lowering action , and to compare their properties for development of hyperlipidemia .Methods Two stocks of the 5-week-old guinea pigs were randomly divided into two groups, normal group (NC) and model group (Model).For the NC group, 12 guinea pigs were fed with normal chew .For the model group , after fed with high-fat diet for four weeks , 24 male guinea pigs were randomly grouped and treated with vehicle (VC group) and pitavastatin (Pit group) calcium, respectively, by gavage as well as received high-fat diet.Before and after modeling and pitavastatin treatment , blood samples were collected and subjected to analysis of plasma TC , TG, HDL-C and LDL-C, respectively .Results In the normal group , the blood lipid levels of albino guinea pigs were more stable than that of the pigmented pigs with the increase of age .After fed with high-fat diet , the plasma lipid levels of TC , TG and LDL-C were significantly increased in the two strains of guinea pigs , while HDL-C showed a decrease to varying degrees .Interestingly , the lipid level in the albino guinea pigs was significantly higher than that of pigment guinea pigs . And also, after drug administration for four weeks , pitavastatin treatment significantly decreased the elevated lipid level of TC, TG and LDL-C in the albino guinea pigs compared with that in the pigment guinea pigs .Conclusions The albino guinea pigs and pigment guinea pigs demonstrate certain differences in establishing dyslipidemic model and evaluating lipid -lowering pharmacodynamics .However , compared with the pigment guinea pigs , the albino guinea pigs have obvious superiority because of easy establishment of hyperlipidemia model and are more sensitive to lipid -lowering drugs .

Adenoma, Villous ; metabolism ; pathology ; surgery ; Aged ; Diagnosis, Differential ; Female ; Humans ; Keratin-20 ; metabolism ; Keratin-7 ; metabolism ; Mullerian Ducts ; pathology ; Papilloma ; pathology ; Vaginal Neoplasms ; metabolism ; pathology ; surgery

Objective To evaluate the association of COX2 genetic variants with the risk of esophageal cancer and the interaction of COX2 genetic variants with Hp infection. Methods A total of 119 patients with esophageal cancer and 238 frequency-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Odds ratios (OR) and 95% confidence intervals ( CI) were estimated by logistic regression. Results Case-control analysis showed an increased risk of developing esophageal cancer for 1195 GA(OR =2.69,95% CI= 1. 46-5. 14) and 1195AA ( OR = 2. 30,95% CI = 1.23-4. 89) genotype carriers,respectively, compared with non 1195 GG carriers. When stratified by Hp status, the significantly increased risk of esophageal cancer was found among Hp carrier with OR (95%CI) =2.74 (1.35-5.96) ,but not among Hp non-carriers. Conclusion Genetic polymorphism in COX2 promoter region may play an important role in esophageal cancer by Hp infection.

Child ; Endoscopy ; Humans ; Male ; Paraganglioma ; surgery ; Urinary Bladder Neoplasms ; surgery

To enhance the quality and efficiency of ozagrel by investigating the differences between the ozagrel polymorphs in bioavailability. Solid ozagrel in different polymorph forms were orally administered to SD rats. An HPLC method was established to determinate plasma level of ozagrel. The bioavailabilities of two polymorph forms were calculated and compared. The pharmacokinetic parameters of ozagrel, were as follows: Cmax was 32.72 ± 17.04 and 34.01 ± 19.13 mg · L(-1), respectively; AUC0-t was 61.14 ± 14.76 and 85.56 ± 18.08 mg · L(-1) · h, respectively; t½ was 1.53 ± 0.51 and 4.73 ± 3.00 h, respectively. There was no significant difference in pharmacokinetic parameters between form I and II polymorphs of ozagrel while the t½ of form II is longer, which indicates that the use of form II polymorph as pharmaceutical product may prolong the effective action time in clinics. This would help the polymorph quality control in drug production.
Animals ; Biological Availability ; Chromatography, High Pressure Liquid ; Methacrylates ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley