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題 名 | 高氏柴胡製備小柴胡湯對糖尿病腎病變之保健功效評估=Effect of Xiao-Chai-Hu-Tang Prepared with Bupleurum kaoi on Diabetic Nephropathy |
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作 者 | 葉靜華; | 書刊名 | 中醫藥年報 |
卷 期 | 3 2014.12[民103.12] |
頁 次 | 頁(49)1-(49)35 |
分類號 | 418.1 |
關鍵詞 | 糖尿病腎病變; 高氏柴胡; 小柴胡湯; 氧化壓力; TGF-β; BMP-7; Diabetic nephropathy; Bupleurum Kaoi; Xiao Chai Hu Tang; Oxidative stress; |
語 文 | 中文(Chinese) |
中文摘要 | 研究目的:糖尿病腎病變已經成為全球嚴重的健康問題,糖尿病腎病變的預防與治療是極為重要的議題。研究中藥治療糖尿病腎病變,進而開發成複合性保健食品有助於降低糖尿病腎病變發生率。高糖產生的活性氧化物 (Reactive oxygen species, ROS)在腎臟引發氧化壓力是造成糖尿糖腎病變的重要因子,高糖造成的氧化壓力會刺激腎臟細胞分泌乙型轉型生長因子 (transforming growth factor-β, TGF-β),促使腎臟細胞產生更多 ROS,並且增加腎臟細胞對 TGF-β的反應性,造成腎臟細胞分泌細胞外間質 (extracellular matrix, ECM) 蛋白,引發腎臟纖維化,降低腎功能;骨誘導蛋白 -7 (bone morphogenetic protein-7, BMP-7)是一個具有腎臟保護功能的蛋白, BMP-7協助維持腎臟細胞正常生理功能以及腎臟組織結構之完整性, BMP-7在初期糖尿病腎病變就會逐漸消失。增加糖尿病大鼠腎臟組織中 BMP-7蛋白表現,有助於降低糖尿病腎病變的腎臟氧化壓力,進而抑制糖尿病腎臟中的 TGF-β分泌以及 ECM蛋白合成。中藥方劑小柴胡湯在保肝、抗發炎、抗腫瘤等研究中已有相當多報導,而此若以台灣特有種 -高氏柴胡製備,則更能增加小柴胡湯的保肝及抗發炎功效,然而,高氏柴胡製備之小柴胡湯是否對糖尿病腎病變具有治療或保健功效卻無相關研究報告。本研究目的在證明小柴胡湯之護腎效果,並釐清其作用機轉與使用安全性,並與高氏柴胡取代北柴胡所配製之小柴胡湯之護腎效果作比較。 研究方法:分別以北柴胡和高氏柴胡兩種小柴胡湯,動物實驗利用 Streptozotocin (STZ)誘導糖尿病腎病變小鼠動物模型,體外細胞實驗利用高糖暴露之腎絲球細胞產生高氧化壓力模式,進行抗氧化與護腎療效評估;連續二十八天灌食兩種小柴胡湯給正常小鼠,進行安全性評估,利用腎臟上皮細胞 (NRK52E cell)進行腎臟細胞毒性試驗。 結果與討論:小柴胡湯(300 mg/kg)對 STZ誘導之第一型糖尿病腎病小鼠之腎功能具有改善的作用。高氏柴胡製備之小柴胡湯 (300 mg/kg)對 STZ誘導之第一型糖尿病腎病小鼠之腎功能具有改善的作用,且效果較小柴胡湯佳。小柴胡湯與高氏柴胡製備之小柴胡湯對於腎臟的保護作用,可能機轉如下: 1. 減少腎臟組織中 TGFβ、 fibronectin、collagen IV等基因表現。 2.增加腎臟保護蛋白 BMP-7基因表現。 3.降低腎臟間質細胞因為高糖所造成之氧化壓力。另外,二十八天安全性評估與腎臟細胞安全性試驗顯示小柴胡湯與高氏柴胡製備之小柴胡湯對腎臟細胞與小鼠全身沒有毒性,最大安全劑量可達 3 g/kg。本研究藉由對於高氏柴胡製備小柴胡湯以及高氏柴胡本身之保護腎臟功能完整評估,證明其對於改善糖尿病腎病變之作用,未來有機會應用在糖尿病腎病的病患。 |
英文摘要 | AIM: Diabetic nephropathy (DN) is a serious health problem thus preventions and therapeutics for DN are important issues. Oxidative stress is one of the factors leading to nephropathy which stimulates renal cells to secrete transforming growth factor-β (TGF-β) and promotes renal cells producing more ROS. Thus renal cells secrete extracellular matrix (ECM) protein which leads renal fibrosis and renal funciton impaired. Bone morphogenetic protein-7 (BMP-7) could maintain renal functions and renal structural integrity in kidney. Traditional Chinese Medicine, Xiao-Chai-Hu-Tang (XCHT), was reported with hepatoprotective, anti-inflammatory, anti-cancer ability. The bioactivities of XCHT remedy, prepared with Bupleurum Kaoi insteaded of Bupleurum chinense DC., KCHT, could be enhanced. This study aimed to clarify whether XCHT and KCHT can prevent DN and whereby the mechanism in streptozotocin-induced diabetic mice and high-glucose exposed mesangial cells (RMC). METHOD: We analyzed the renal protective effect of XCHT and KCHT during DN in STZ-induced diabetic mice. The expression of TGF-β, fibronectin, collagne IV and BMP-7 in the kidney of STZ-induced diabetic mice and huigh glucose exposed RMC was detected by RT-PCR and western blot. The anti-oxidative effect of XCHT and KCHT was also analyzed in vivo and in vitro. We also examined the in vivo 28-days safety examination and in vitro cytotoxity of XCHT and KCHT. RESULTS & DISCUSSION: XCHT and KCHT were orally administrated to streptozotocin (STZ)-induced diabetic mice and treated to high glucose (HG) exposed rat mesangial cell (RMC). After 4-week treatment, both XCHT and KCHT improved renal functions and renal hypertrophy in STZ-diabetic mice. The expression of TGF-β1, fibronectin, and collagne IV was decreased but expression of BMP-7 expression was increased in STZ-diabetic mice and HG exposed RMC. The DPPH assay showed that XCHT and KCHT could scavenge free radicals. DHE stain and CM-H2DCFDA analysis indicated that XCHT could inhibit high glucose-induced ROS in RMC. These results suggest that XCHT and KCHT have ability to improve renal functions in STZ-diabetic mice through decreasing oxidative stress, TGF-β1, fibronectin, and collagen IV production in kidney during the development of diabetic nephropathy. The results of 28-days safety examination and cytotoxity promised the using safety of XCHT and KCHT. The present study suggests that XCHT and KCHT could be applied to improve renal functions in diabetic disorders. |
本系統中英文摘要資訊取自各篇刊載內容。