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Expression of Hypoxia-Inducible Factor-1α in the Internal Spermatic Vein of Rats with Experimentally Induced Left Varicocele

以實驗誘導左側精索靜脈曲張的老鼠探討缺氧誘發因子-1α(HIF-lα)在內精索靜脈的表現

摘要


研究目的:左側精索靜脈曲張的病人,已被發現在內精索靜脈中有較高的缺氧誘發因子-lα(HIF-lα)的表現量;所以本文利用實驗誘導出左側精索靜脈曲張的老鼠,探討其內精索靜脈是否有與病人相同的情形發生。 材料與方法:以24隻Sprague-Dawley成鼠做左側部分腎靜脈的結紮當實驗組,另外16隻進行假手術當對照組,分別在術後的二、四、八及十二週取下兩組的內精索靜脈進行缺氧誘發因子-lα的分析比較。 結果:精索靜脈曲張的老鼠(實驗組)在術後的第二、四及八週缺氧誘發因子-1α(HIF-lα)的表現量均大於對照組,且有統計意義,直到第十二週的代償期來臨。 結論:缺氧誘發因子-lα在內精索靜脈的表現量增加,在病人及實驗的老鼠均有劃固現象,證明缺氧的病生理反應是存在精索靜脈曲張的疾病;而進一步改善睪丸的缺氧情形及使用缺氧誘發因子-lα的抑制劑是否可以降低精索靜脈曲張病人手術後的復發率,則猶待未來的探討。

並列摘要


OBJECTIVE: Increased expression of hypoxia-inducible factor-la (HIF-1α) in the internal spermatic vein (ISV) of patients with varicocele was recently reported. In this study we investigated whether the same result occurs in the ISV of rats with experimentally induced left varicocele (ELV). MATERIALS AND METHODS: ELV was created by partial ligation of the left renal vein in 24 adult male Sprague-Dawley rats. An additional 16 rats that underwent a laparotomy and renal vein handling without ligation served as the sham control group. Rats were sacrificed at 2, 4, 8, and 12 weeks following varicocele creation. The ISV was harvested to measure the expression of HIF-1α by immunoblotting. RESULTS: HIF-1α immunoblots from both the control and varicocele rats revealed a single band. The relative intensities of HIF-1α protein at 2, 4, 8, and 12 weeks were 51.14±9.53, 65.94±12.98, 70.38±21.29, and 66.07±15.29 in the control group, and 162.63±16.77, 245,24±37.02, 200.52±33.36, and 85.82±26.09 in the varicocele group, respectively. CONCLUSIONS: Expression of HIF-1α in the ISV of rats with a varicocele was significantly higher than that of rats in the control group, especially at 2, 4, and 8 weeks after varicocele creation, but not in the compensatory stage which occurred in the 12th week. This suggests that hypoxic pathophysiological changes occur in the ISV of rats with ELV. This is also compatible with the same hypoxic occurrence in the ISV of patients with varicocele. Additional studies are needed to investigate whether the reduction in testicular tissue hypoxia and the inhibition of HIF-1α can decrease the chance of varicocele recurrence in patients in the future.

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