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Objective To explore the mechanism underlying a selective liver nitric oxide donor V-PYRRO/NO effects on the gene expression of LTC4 synthase(LTC4S) during hepatic ischemia reperfusion(I/R).Methods Adult male SD rats were divided into 3 groups:control group(sham),ischemic-reperfusion group(I/R) and V-PYRRO/NO group. Liver subjected to 1 hour of partial hepatic ischemia followed by 5 hours of reperfusion, saline or V-PYRRO/NO[1.06 mmol/(kg·h)] administered intravenously. The mRNA expression of LTC4S in rat liver was examined by RT-PCR method,the protein expressions of NF-κB p65,p50 and IκB in liver cell lysates and nu-clear extracts were detected by Western blot analysis. Results Hepatic mRNA expression of LTC4S in I/R group was higher than that in sham group(P<0.05), whereas it was lower in V-PYRRO/NO group than that in I/R group(P<0.05). Moreover,compared with sham group,the protein expressions of NF-κB p65 and p50 in nucleus extract were markedly increased(P<0.01) but significantly decreased in cytoplasm(P<0.01) in I/R group. V-PYRRO/NO reversed completely the increase of these protein expressions in nucleus extract (P<0.05) and the decrease of them in cytoplasm(P<0.01,P<0.05) during hepatic I/R injury.However,IκB protein in three groups did not change. Immunohistochemistry staining revealed that no marked positive staining for NF-κB p65 was found in sham liver,I/R liver exhibited strong cytoplasmic and nuclear positive staining for NF-κB p65,but V-PYRRO/NO I/R group liver presented slight cytoplasmic and nuclear staining. Conclusions V-PYRRO/NO may down-regulate LTC4S mRNA expression by inhibiting NF-κB activation independent of IκB during hepatic I/R injury.
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@#According to “2015 State of Innovation” released by Thomson Reuters, China Pharmaceutical University ranked the first in the field of heterocyclic compounds in 2010-2014 among innovation agencies in Asia. In order to fully understand the situation of the new drug research of this university, this paper analyzes its patent application from 2010 to 2014 in the field of heterocyclic compounds. The key applications were summarized. In summary, this university showed its advantage of high filings and high licensing rate in the field of heterocyclic compounds, yet with the shortcomings of low patent applications in PCT. Furthermore, suggestions have been made for the intellectual property management of this university.
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Aim: To explore the in situ intestinal absorption in rats of ZLR-8, an insoluble NO-donor drug, and to compare the intestinal absorption enhancement by spray-dried emulsion. Methods: Intestine of rats was cannulat-ed for in situ perfusion. UV and HPLC methods were used to monitor phenolsulfonphthalein and ZLR-8, respec-tively. The effects on ZLR-8 absorption of the intestinal segments, the concentration of ZLR-8 and the pH of the circulating perfusate were studied. The absorption of ZLR-8 suspension was compared to that of the spray-dried emulsion. Results: 1-h in situ intestinal perfusion of the spray-dried emulsion allowed the estimation of the absor-tion percentage to be (23. 54 ± 1. 40) %, (15. 95 ± 0. 09) %, (12. 30 ± 0. 74) %, (3. 98 ± 0. 12) %, respec-tively; the absorption rate constants in duodenum, colon, jejunum and ileum to be (0.248 6 ±0.046 0) h~(-1), (0. 143 7 ±0. 036 0) h~(-1), (0. 069 2 ±0. 001 3) h~(-1), (0. 020 8 ±0. 000 4) h~(-1), respectively. Significant differ-ences in absorption characteristics were found among intestinal segments. In the range of 3. 4-9. 4, pH of the per-fuate had significant influence on the absorption of ZLR-8, and better absorption appeared at pH of 5. 4 to 7. 4. It was found that the absorption rate constant was unaffected by ZLR-8 concentration. However, the absorption amount was proportional to ZLR-8 concentration. Compared to the ZLR-8 suspension, the in situ intestinal absorption of ZLR-8 in rats given the spray-dried emulsion increased significantly. Conclusion: It was only found that ZLR-8 administered in suspension has minor absorption in rat duodenum while no apparent absorption occurred in other segemnts. ZLR-8 in spray-dried emulsion was fairly absorbed in the rat intestinal segments. Passive diffusion was invloved in the absorption of ZLR-8. Spray-dried emulsion significantly enhanced the intestinal absorption of ZLR-8 in rats.