T of PRF1 gene was found.There was a strong linkage disequilibrium among the SNPs of GZMB.Conclusion:7 SNPs were detected in PRF1 and GZMB genes all together,two of which were first identified. There is apparent linkage disequilibrium among SNPs of PRF1and GZMB gene in Han population of Chongqing.

Objective To investigate the therapeutic effects of emodin on acute cholestatic hepatitis and mec-hanism thereof. Methods Fifty Sprague - Dawley (SD)rats were randomly divided into 5 groups and were treated with emodin,ursodeoxycholic acid,dexamethasone,or normal saline respectively for 4 days. On the fifth day gastric perfusion of alpha - naphthylisothiocyanate(ANIT)was performed to establish models of choiestatic hepatitis. Four to six hours after the establishment of model the above mentioned agents were given continuously. Forty - eight hours after the model establishment blood samples were collected from abdominal aorta to examine the total bilirubin(TB),direct bilirubin (DB),alanine aminotransferase(ALT),total bile acid(TBA),aspartate aminotransferase(AST),alkaline phosphatase (ALP),gamma glutamine transferase(GGT). Specimen of liver was collected to undergo pathological examination. Real - time PCR was used to detect the mRNA expression of farnesoid X receptor(FXR),small heterodimer partner (SHP ),bile salt export pump (BSEP ),uridine diphosphate glucuronosyltransferase 2 family polypeptide B4 (UGT2B4). Results The serum levels of total bilirubin (TB),direct bilirubin (DB),alanine aminotransferase (ALT),total bile acids (TBA),aspartate aminotransferase (AST),and alkaline phosphatase (ALP)of the model group were respectively (68. 1 ± 26. 1)μmol/ L,(46. 3 ± 20. 1)μmol/ L,(483 ± 228)U/ L,(159. 1 ± 57. 9)μmol/L,(2. 0 ± 0. 5)U/ L,(996 ± 382)U/ L,(324 ± 120)U/ L. The levels of TB,DB,ALT,TBA,AST,ALP of the emodin group were respectively (15. 0 ± 8. 7)μmol/ L,(10. 8 ± 3. 9)μmol/ L,(147 ± 71)U/ L,(60. 1 ± 22. 7)μmol/ L, (295 ± 104)U/ L,(222 ± 59)U/ L,and were all significantly lower than those of the model group (all P < 0. 05). The levels of TB,DB,ALT,TBA,AST,GGT,ALP of the emodin group were all significantly lower than those of the ursode-oxycholic acid group (all P < 0. 05). The levels of TB,DB,ALT,TBA,GGT,AST were all significantly lower than those of the dexamethasone group (all P < 0. 01). The expression levels of FXR,SHP,BSEP,UGT2B4 mRNA in the emodin group (1. 087 ± 0. 285,0. 892 ± 0. 390,0. 902 ± 0. 149,1. 785 ± 0. 403)were all significantly higher than those of the model group (0. 152 ±0. 088,0. 559 ±0. 194,0. 561 ±0. 123,0. 177 ±0. 039,all P <0. 05). Conclusions By decreasing the levels of TB,DB,ALT,TBA,AST,ALP and reducing pathological changes,emodin has a protective effect on cholestatic hepatitis. It has better effects than ursodeoxycholic acid and dexamethasone. These effects may be due to promoting FXR,SHP,BSEP and UGT2B4 expression.

OBJECTIVES: Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke. Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury. However, plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke. This study aims to explore the role of delayed recanalization on blood-brain barrier (BBB) in the penumbra (surrounding ischemic core) and neurological outcomes after middle cerebral artery occlusion (MCAO). METHODS: Recanalization was performed on the 3rd day after MCAO. BBB disruption was tested by Western blotting, Evans blue dye, and immunofluorescence staining. Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO. The expression of fibroblast growth factor 21 (FGF21), fibroblast growth factor receptor 1 (FGFR1), phosphatidylinositol-3-kinase (PI3K), and serine/threonine kinase (Akt) in the penumbra were observed by immunofluorescence staining and/or Western blotting. RESULTS: The extraversion of Evans blue, IgG, and albumin increased surrounding ischemic core after MCAO, but significantly decreased after recanalization. The expression of Claudin-5, Occludin, and zona occludens 1 (ZO-1) decreased surrounding ischemic core after MCAO, but significantly increased after recanalization. Infarct volume reduced and neurological outcomes improved following recanalization (on the 7th day after MCAO). The expressions of Claudin-5, Occludin, and ZO-1 decreased surrounding ischemic core following MCAO, which were up-regulated corresponding to the increases of FGF21, p-FGFR1, PI3K, and p-Akt after recanalization. Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K, p-Akt, Occludin, Claudin-5, and ZO-1 in the penumbra, which weakened the beneficial effects of recanalization on neurological outcomes after MCAO. CONCLUSIONS Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway, which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats.
Animals ; Rats ; Blood-Brain Barrier/metabolism* ; Brain Ischemia ; Claudin-5/metabolism* ; Infarction, Middle Cerebral Artery/metabolism* ; Ischemic Stroke/metabolism* ; Occludin/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Reperfusion Injury/metabolism*