Hypertension：Epo-受体产品抑制促红细胞生成素诱导高血压
生物谷：8月的《高血压》（Hypertension 2007;50:439-445.）杂志上报告，在小鼠研究中，基因工程产品促红细胞生成素结合蛋白(Epo-bp)和抗Epo-bp抗体，显示可以预防促红细胞生成素诱导的高血压，不影响红细胞压积。
明尼苏达大学的Jong Y. Lee博士说，由于高血压是促红细胞生成素治疗的最显著的并发症，“所以我们纯化的促红细胞生成素受体物质的临床意义是多样的。”研究者研究了被给予促红细胞生成素、Epo-bp和Epo-bp抗体或生理盐水注射液每周2次共4周的大鼠。
与盐水相比，红细胞压积在促红细胞生成素组显著增加，但是在基因工程产品组或盐水组无改变。同样，血压只在促红细胞生成素组升高。研究者发现，使用Epo-bp和抗Epo-bp抗体与促红细胞生产素治疗，对促红细胞生成素诱导的红细胞压积增加几乎无影响。另一方面，当促红细胞生成素与Epo-bp或抗Epo-bp抗体一起被给予时，血压维持在与盐水组类似的水平。
研究组总结说，Epo-bp和抗Epo-bp抗体可消除促红细胞生成素诱导的高血压，不影响红细胞压积和血容量。Lee博士补充说，他们还使用这些产品开发了试剂盒，作为促红细胞生成素或促红细胞生成素受体相关疾病的鉴别诊断工具。（援引医业网）
原始出处:
Hypertension. 2007;50:439.
Prevention of Erythropoietin-Associated Hypertension
Mary S. Lee; John S. Lee; Jong Y. Lee
From the School of Medicine (M.S.L.), Northwestern University, Chicago, Ill; and the Department of Medicine (J.S.L., J.Y.L.), University of Minnesota School of Medicine, Minneapolis.
Hypertension is the most significant complication from treatment with erythropoietin (Epo). Can Epo-induced hypertension be eliminated? We examined systemic and local effects of our genetically engineered products, Epo-binding protein (Epo-bp) and anti–Epo-bp antibodies, on randomly assigned Sprague–Dawley rats at midnight, 4 AM, 8 AM, noon, 4 PM, and 8 PM. Blood pressure, hematocrit, and body weight were measured immediately before and after the completion of a 4-week, twice-weekly course of Epo (50 U/kg), Epo-bp, anti–Epo-bp antibodies, or physiological saline injections. Epo treatment increased hematocrit markedly overall as compared with the saline, Epo-bp, and anti–Epo-bp antibody groups (0.616 versus 0.427, 0.439, and 0.441, respectively) and at each of the 6 test times (all P<0.0001). Epo-bp and anti–Epo-bp antibody treatment with Epo had almost no effect on the Epo-induced hematocrit increase (0.616 versus 0.580 or 0.591, respectively). Circadian blood pressures for Epo versus saline, Epo-bp, and anti–Epo-bp antibody groups were 136.2±2.3 versus 116.2±1.7, 118.4±2.1, and 116.6±2.1 mm Hg, respectively (each P<0.0001). Significantly increased blood pressure was detected at noon, 4 PM, 8 PM, and midnight in Epo treatment. When Epo was given with Epo-bp or anti–Epo-bp antibodies, blood pressure was maintained at similar levels as in saline treatment (each P<0.0001) as compared with Epo treatment alone. Overall, body, brain, and heart weights were significantly lower in Epo treatment than those of other groups. Thus, Epo-bp and anti–Epo-bp antibodies eliminate Epo-induced hypertension without affecting hematocrit and blood volume.
Key Words: erythropoiesis • erythropoietin-binding protein • circadian effects • hypertension • splenomegaly • cardiovascular parameters
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