Background. Thromboxane (TX) A2 inhibition or prostaglardin (PGI2) infusion prevents ischemic acute renal failure (ARF) in animal models. However, the pathophysiological roles of the prostanoid
receptors in the development of ischemic ARF are not fully understood, partly because of the limited specificity of their
inhibitors or antagonists.
Methods. We investigated whether targeted disruption of the PGI2 receptor (IP) or TXA2 receptor (TP) genes conferred susceptibility to renal ischemic-reperfusion injury, using IP and TP knockout mice.
Results. Serum creatinine concentration in TP knockout mice was not significantly different from that in wild-type controls. There
were no significant histological differences between TP knockout and wild-type mice. Likewise, IP knockout mice showed no
significant differences from the wild-type controls in regard to creatinine concentration or histological damage.
Conclusions. Lack of TP or IP had no influence on postischemic ARF in mice, indicating that receptors for TXA2 or PGI2 may have minimal roles in the development of this mouse model of ischemic ARF.
Received: July 5, 2001 / Accepted: April 8, 2002 相似文献
Familial incontinentia pigmenti (IP) is a rare X-linked dominant disorder that affects ectodermal tissues. Over 90% of IP carrier females have a recurrent genomic deletion of exons 4-10 of the NEMO (IKBKG-IKKgamma) gene, which encodes a regulatory component of the IkB kinase complex, required to activate the NF-kB pathway. In IP, mutations in NEMOlead to the complete loss of NF-kB activation creating a susceptibility to cellular apoptosis in response to TNF-alpha. This condition is lethal for males during embryogenesis while females, who are mosaic as a result of X-inactivation, can survive. Recently, a second nonfunctional copy of the gene, DeltaNEMO, was identified, opposite in direction to NEMO in a 35.5-kb duplicated sequence tract. PCR-based detection of the NEMO deletion is diagnostic for IP disease. However, we present instances in which ex 4-10 DeltaNEMO pseudogene deletion occurs in unaffected parents of two females with clinically characteristic IP. These were missed by the currently standard PCR-based method, but can be easily discriminated by a new PCR-based test reported here that permits unambiguous molecular diagnosis and proper familial genetic counseling for IP. 相似文献
A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting. 相似文献
We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5′-nucleotidase which plays a key role in the IP-induced cardioprotection.
BACKGROUND
The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects.
METHODS
Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5′-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure.
RESULTS
This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5′-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold).
CONCLUSIONS
Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5′-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5′-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP. 相似文献