植物萃取物HN242對高血糖引起之腎臟病變的預防與保護作用

Prevention and protection effects of a plant extract HN242 on hyperglycemia-induced kidney disease

賴欣妤(Shin-Yu Lai)

指導教授 ： 龔秀妮

國立臺灣大學/醫學院/解剖學暨細胞生物學研究所/碩士(2016年)

https://doi.org/10.6342/NTU201602766

摘要

糖尿病是21世紀盛行率增加最快的代謝性疾病，根據世界衛生組織(WHO)統計全球目前糖尿病患者約有一億五千萬人，到2025年全球糖尿病患將增加為原本的一倍以上；糖尿病又分第一型(Insulin-dependent diabetes mellitus，IDDM)及第二型(Non- insulin-dependent diabetes mellitus，NIDDM)，由於現代飲食精緻化，罹患率增加的型態主要為第二型。台灣國民健康署指出，近年來糖尿病死亡率位居國人十大死因的前五名，其死亡原因不外乎是糖尿病導致的併發症：腎臟、心血管、神經病變等，而其中腎病變是導致死亡的主要併發症。
腎臟由許多不同種類的細胞組成，由腎絲球過濾單位(血管內皮細胞、基底膜、足細胞)、間質細胞及腎小管細胞維持腎臟的過濾代謝功能，糖尿病會導致腎臟細胞產生異常變化；在前人研究中得知糖尿病腎病變特徵主要為間質細胞擴張、變形及足細胞喪失貼附功能、肥大…等等使腎臟失去原有的過濾功能。
已有文獻證明在腎臟損傷成因中，氧化壓力的提高最為重要，本論文的研究目的是探討由一種樹皮中萃取出來的天然聚合物HN242在高脂飲食環境下是否能透過對抗氧化壓力，達到預防及治療糖尿病腎病變的效果。
本篇研究中使用長時間餵食高脂肪食物之模式誘發C57BL/6小鼠產生第二型糖尿病，預防組為吃高脂飼料同時餵食HN242；治療組為吃高脂飼料一段時間，測定血糖確診高血糖後再餵食HN242。透過腎臟組織切片染色及血液尿液分析等體內實驗及利用MES13腎間質細胞做體外實驗證實，HN242確實可以透過抗氧化及抗發炎等途徑達到保護及修復腎臟細胞的效果。因此，我們確信HN242對預防及治療高血糖導致之腎臟病變具極高的潛力。

關鍵字

HN242 ； 高脂飲食 ； 糖尿病 ； 腎病變 ； 腎臟間質細胞 ； 抗氧化

並列摘要

The growing rate of diabetes mellitus (DM) is the highest in all the metabolic diseases in the 21st century. According to World Health Organization (WHO), there are about 150 million people with diabetes nowadays, and it is also the 5th leading death in 2014 in Taiwan according to the statistic of Ministry of Health and Welfare.
Two types of diabetes mellitus are defined. Type 1 diabetes (Insulin-dependent diabetes mellitus，IDDM) is usually diagnosed in children and teenagers who do not produce insulin. Type 2 diabetes (Non- insulin-dependent diabetes mellitus，NIDDM) is characterized by insulin resistance, and many lifestyle factors are known to be important in developing type 2 diabetes, including obesity. Patient with diabetes develops various complications that might cause death, and the major one is diabetic nephropathy.
Kidney participates in whole-body homeostasis through filtration, reabsorption, and secretion, which take place in the nephron. Mesangial cells, podocytes and tubular epithelial cells play important roles in nephrons. Diabetic nephropathy leads to mesangial cell hypertrophy, podocyte loss and tubular epithelial cell damage or apoptosis, which results in filtration membrane failure and reabsorption dysfunction.
The cause of diabetic nephropathy is well known for oxidative stress increase. This study aims to study whether HN242 , a nature compound extracted from the bark of tree in South America, can protect kidney from hyperglycemia-induced kidney disease by anti-oxidant ability.
In the in vivo mouse model, HN242 was used to co-treat or post-treat with high-fat-diet for 70 or 35 days. With series of morphological observations, HN242 can decrease hyperglycemia-induced kidney damages, including basement membrane thicken, mesangial cell expansion, and podocyte process detachment. The filtration function loss of kidney caused by hyperglycemia is also recovered by HN242, and the reduction of inflammation and oxidative stress also be observed in kidney. For better dissection of the signaling pathway underlying how HN242 protects kidney from high fat-induced diabetes nephropathy, palmitate acid (PA) is used to treat MES 13 mouse mesangial cells in the in vitro cell model. HN242, either co-treat or post-treat with PA administration, can block the damages caused by PA through upregulating the anti-oxidant and anti-inflammation abilities.
In conclusion, we suggest that HN242 may have great potential for both preventive and therapeutic use for diabetic nephropathy.

並列關鍵字

HN242 ； High fat diet ； Diabetes ； Nephropathy ； MES13 ； Anti-oxidant

參考文獻

62. 呂金盈, 腸泌素在第二型糖尿病治療的角色. 內科學誌, 2011. 22: p. 401-408.

64. 陳建良, 陳., 糖尿病腎病變. 腎臟與透析, 2005. 17: p. 117-122.

2. Magill, S.B., Acarbose for the prevention of diabetes. Cleve Clin J Med, 2003. 70(12): p. 1088; author reply 1088.

4. Thomas, M.C., et al., Diabetic kidney disease. Nat Rev Dis Primers, 2015. 1: p. 15018.

5. Guyton, A.C.H., John E, Textbook of Medical Physiology. 2006: p. 316–317.