| 摘要: | 在老化的過程中，因增齡而引起的中樞神經系統退化，已知部分原因與腦部產生活性氧而造成的細胞毒有關。所以有許多具有抗氧化作用的合成及天然物質被試著使用來預防因增齡而引起的中樞神經系統退化。我們研究室先前的研究發現人尿製劑具有很好的氫氧自由基清除作用。本實驗目的是使用老年雄性大鼠和去卵巢大鼠，來評估人尿製劑對老化的指標如如脂質過氧化反應、穀胱甘?及超氧化物歧化?的影響。另外，也探討人尿製劑對去卵巢大鼠引起的骨質疏鬆，及對cisplatin引起的腎毒性的影響。得到的結果如下： 1. 十五月齡的雄性大鼠，給予含人尿製劑 0.2 % 及1 %的飲水連續八個月。結果顯示，人尿製劑處理的大鼠，大腦皮質、血漿、主動脈、睪丸中的丙二醛濃度比控制組低。人尿製劑處理的大鼠，肝臟和腎臟的穀胱甘?濃度顯著增加。另外，人尿製劑處理的大鼠，皮膚和腎臟氫脯氨酸含量明顯減少。 2. 去卵巢大鼠口服人尿製劑八週。不加鐵誘發丙二醛的濃度，在去卵巢大鼠組的大腦皮質、海馬迴、肝臟、心臟、子宮及腎上腺較偽手術組高，但在紋狀體二組無差異。人尿製劑處理的大鼠，對大腦皮質、海馬迴、紋狀體、腎上腺的不加鐵誘發丙二醛濃度，與控制組比較有減少作用。但對肝臟、心臟、子宮則無影響。加鐵誘發丙二醛的濃度，在去卵巢大鼠的大腦皮質、海馬迴、肝臟、心臟、子宮及腎上腺較偽手術組高。人尿製劑處理的大鼠，對海馬迴、紋狀體的加鐵誘發丙二醛濃度，與控制組比較有減少作用，但對大腦皮質、肝臟、心臟、子宮及腎上腺則無影響。在去卵巢大鼠的大腦皮質中，穀胱甘?含量，超氧化物歧化?、過氧化氫?和穀胱甘?過氧化?的活性與偽手術組比較沒有差異，人尿製劑處理的大鼠，大腦皮質的穀胱甘?過氧化?活性下降，但對超氧化物歧化?、過氧化氫?的活性及穀胱甘?的濃度沒有影響。 3. 大鼠分成偽手術組及去卵巢手術組，去卵巢大鼠放置十二週讓其形成骨質流失的狀態。在去卵巢手術後十二週，給予人尿製劑治療，於手術後二十週將大鼠犧牲。去卵巢大鼠和偽手術組比較有骨質疏鬆的情況，在股骨及第四腰椎的密度骨、灰份及鈣含量明顯下降。人尿製劑能降低去卵巢後所產生的影響。另外，人尿製劑對去卵巢大鼠的陰道及子宮有增重作用。這些結果顯示人尿製劑經由刺激雌激素接受體來改善去卵巢所誘發的骨質疏鬆。 4.大鼠先給予人尿製劑五天，第五天大鼠靜脈注射cisplatin ( 5mg/kg i.v.)，而後再給人尿製劑三天。人尿製劑可以顯著的改善cisplatin所引的腎毒性。人尿製劑明顯改善cisplatin所引起的腎毒性，可從血清中血液尿素氮和肌酸肝明顯下降，以及明顯增加尿量和肌酸肝清除率看出。人尿製劑可增加經cisplatin排空的腎臟總均漿及粒線體層中的穀胱甘?量。這些發現顯示，人尿製劑增加穀胱甘?的含量，參與人尿製劑對cisplatin誘發腎毒性的保護作用。 我們的研究結果顯示，人尿製劑可經由抗氧化作用，減緩老化的過程。本研究亦證實人尿製劑對於骨質疏鬆症是有益的。另外，人尿製劑可以對抗cisplatin所引起的腎毒性，顯示人尿製劑也許可以應用在cisplatin的化學療法。; During aging processes, it is believed that the age-related deterioration of the central nervous system is partly due to the cytotoxicity of reactive oxygen species generated in the brain. Thus, various synthetic or natural compounds having antioxidative properties have been tried to protect against the age-induced deterioration of CNS. In our previous works, we showed that a preparation of human urine (PHU) is a good scavenger of hydroxyl radical. The aim of this experiment was to evaluate the effects of PHU on the age-related parameters, such as lipid peroxidation (LPO), glutathione (GSH). and superoxide dismutase (SOD), in aged male rats and ovariectomized (OVX) rats. In addition, effect of PHU on the osteopenia in OVX rats, and nephrotoxicity induced by cisplatin were also studied. The following results were obtained. 1.The rats (15 months) were received PHU 0.2 or 1.0 g/dl drink water for 8 months. The results showed that MDA concentrations of brain cortex, plasma, aorta, testis were significantly lower in the PHU treated group as compared with the control group. The concentrations of GSH were significantly increased in the liver and kidney of rats treated with PHU. In addition, the diminution of hydroxyproline of skin and kidney in PHU treated rats were also observed. 2.The OVX rats were orally administered PHU for 8 weeks. Fe-independent MDA concentrations in brain cortex, hipocamppus, liver, heart, uterus and adrenal gland, but not in striatum, increased significantly in OVX controls compared to sham-operated rats. Fe-independent MDA concentrations in brain cortex, hipocamppus, striatum and adrenal gland, but not in liver, heart and uterus, decreased significantly in OVX rats treated with PHU compared to those in OVX rats. Fe-dependent MDA concentrations in brain cortex, hippocampus liver, heart and uterus, but not in striatum and adrenal gland, increased significantly in OVX controls compared to sham-operated rats. Fe-dependent MDA concentrations in striatum and hippocampus, but not in brain cortex, liver, heart, uterus and adrenal gland, decreased significantly in OVX rats treated with PHU compared to those in OVX controls. GSH contents and activities of SOD, catalase and GSH-Px of brain cortex were not significantly between the sham-operated group and OVX controls. However, PHU suppressed the activity of GSH-Px, but not SOD and catalase, in the brain cortex of OVX rats. 3.The rats were divided into the sham and OVX groups. The OVX rats were allowed to loss bone for 12 weeks. At 12 weeks post-OVX, the OVX rats were treated with PHU. They were killed 20 weeks p |
