Effect of valsartan on the expression of angiotensin II receptors in the lung of chronic antigen exposure rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Many studies have suggested that angiotensin II (Ang II) and its receptors may be involved in the development of asthma. However, the expression of angiotensin II receptors (AGTR) is not clear in the lung tissue of chronic asthmatics. This study was designed to determine the relationship between airway remodeling, dysfunction and the expression of AGTRs in a rat model of asthma.</p><p><b>METHODS</b>Rats were sensitized with ovalbumin (OVA) for 2 weeks. Sixty minutes before an inhalation challenge, the rats were pretreated either with valsartan (15, 30, 50 mg x kg(-1) x d(-1)) or saline intragastrically. Then the rats received an OVA challenge for 30 alternative days. Acetylcholine (Ach)-induced bronchoconstriction was measured after the final antigen challenge. White cell counts in bronchoalveolar lavage fluid (BALF) and morphological changes in the airways were then assessed. The levels of transforming growth factor-beta 1 (TGF-beta(1)) and platelet-derived growth factor (PDGF) in BALF were detected by ELISA. The levels of AGTR1 and AGTR2 mRNA and protein in lung tissues were measured by RT-PCR and Western blotting.</p><p><b>RESULTS</b>AGTR1 mRNA and protein levels in repeatedly OVA-challenged rats were significantly increased as compared with negative controls. The AGTR1 mRNA expression versus white cell counts of BALF and airway wall thickness (mainly in small airways) in lungs of chronic antigen-exposed rats were positively correlated. Valsartan decreased the level of AGTR1 in repeatedly OVA-challenged rats. However, AGTR2 mRNA and protein levels in the OVA-challenged rats and high-dose valsartan-treated rats (50 mg x kg(-1) x d(-1)) were also increased. Valsartan significantly decreased inflammatory cell accumulation and attenuated Ach-evoked bronchoconstriction in repeatedly antigen-challenged rats. Valsartan also decreased allergen-induced structural changes in rat airway (including total airway wall thickness and smooth muscle area) and the levels of TGF-beta(1) and PDGF in BALF.</p><p><b>CONCLUSIONS</b>AGTR1 expression is potentially associated with airway remodeling and dysfunction in asthma. Ang II and AGTR1 may participate in airway inflammation and airway remodeling of chronic antigen-exposed rats. Valsartan, a AGTR1 antagonist, could inhibit AGTR1 expression and partially inhibits structural airway changes as well as airway inflammation in chronic OVA-exposed rats.</p>

Preparation and cultivation of microencapsulated recombinant CHO cells / 生物工程学报

Transplantation of the microencapsulated recombinant cells is a novel alternative approach to gene therapy of tumors. The semi-permeable membrane of microcapsule protects cells from host's immune rejection, increases the efficiency of gene transfer and reduces the need for frequent injection. Optimization of the preparation and culture is needed to acquire biological microcapsule with high cell viability and protein production. In this work, we studied the effect of different preparation and culture condition on the microencapsulated recombinant CHO cells growth and endostatin production. The result showed that the inoculum cells growth phase and seeding density potently affected the growth and endostatin production of the recombinant CHO cells in the microcapsule. The exponential growth phase recombinant CHO cells with a seeding density of 1 x 10(6) - 2 x 10(6) cells/ mL microcapsules benefited to the cells growth and endostatin production. The time of preparation was another important effect factor of cells viability, the cells viability decreased with the increase of preparation time and the time of preparation should be under 5h for maintaining the cell viability and endostain production. The highest viable cell density and endostatin production was acquired when the microcapsule percentage was 5% in the culture of the microencapsulated cells, the cell growth and endostatin production decreased with the increase of the microcapsule percentage.

Effect of the in vitro culture and cryopreservation on the growth of the microencapsulated recombinant cell and endostatin production / 生物工程学报

Microencapsulated recombinant cells technology is a novel approach to tumors therapy. It is necessary to prepare a plenty of the microcapsules with better cell viability and higher endostatin production in order to bring this technology into the clinic. The in vitro culture and cryopreservation are very important parameters in the preparation of microencapsulated cells. In this work, we studied the effect of the in vitro culture and cryopreservation on microencapsulated recombinant cells growth and endostatin production and the effect of the in vitro culture on the cryopreservation of microencapsulated recombinant cells. The results showed that the time of in vitro culture potently affected microencapsulated recombinant CHO cells growth in vivo, endostatin production and the microcapsule stability. The microcapsule kept intact after 36 days of implantation when the in vitro culture time was under 4 days. The thawed microencapsulated recombinant CHO cells had better cell growth and higher endostatin production after 40 days of cryopreservation when the in vitro culture time was 4 days and 8 days. Therefore, the best in vitro culture time was 4 days according to the results of the in vivo culture and cryopreservation and the cryopreservation did not affect microencapsulated recombinant CHO cells growth in vivo, endostatin production and the microcapsule stability.