熊果酸对1型糖尿病小鼠肾脏病变的影响

发布时间：2018-01-29 01:20

本文关键词： 糖尿病肾脏病变 STAT MAPK 熊果酸　出处：《广东医学》2017年08期 　论文类型：期刊论文

【摘要】：目的探讨熊果酸对于链脲佐菌素(STZ)诱导的1型糖尿病小鼠肾脏病变的影响及其作用机制。方法将雄性C57BL/6小鼠随机分为糖尿病组和非糖尿病组。用STZ诱导1型糖尿病。非糖尿病组小鼠用等体积的0.1 mol/L柠檬酸溶液进行相应的腹腔注射。在STZ腹腔注射7 d后,测定血糖。将糖尿病组小鼠再随机分为给药组和非给药组。给药组以熊果酸按0.01%(药物质量/食物质量)与粉状动物食物混合均匀后,挤压成块后无摄取限制地喂食糖尿病小鼠。出生3周的雄性C57BL/6小鼠,随机分成两组:一组用低脂食物喂养,另一组用高脂食物喂养。喂养20周时,测定糖耐量和胰岛素耐量实验。以C57BL/6为背景的雄性小鼠分为两组:一组为db~(-/-)(基因突变引起的2型糖尿病)小鼠,一组为相同鼠龄的C57BL/6背景的普通小鼠。在小鼠满12周鼠龄时处死。检测糖尿病小鼠肾脏皮质中与病变相关的多种基因的信使RNA水平的变化;检测高脂食物喂养的肥胖型小鼠和db~(-/-)小鼠肾脏皮质中上述信号通路的变化情况。结果 0.01%的熊果酸喂养1型糖尿病小鼠12周后,可以显著降低由糖尿病引起的Ⅳ型胶原在肾小球中的堆积,并减少由糖尿病引起的肾小球肿大现象。与非糖尿病组小鼠相比,糖尿病组小鼠的lamininα、MCP-1的信使RNA水平都有显著升高,但对糖尿病小鼠喂食熊果酸后对升高的lamininα和MCP-1信使RNA水平并没有影响。与STZ诱导的1型糖尿病小鼠相似,在高脂喂养的肥胖型小鼠肾皮质中STAT3、ERK1/2和JNK也被激活;但在db~(-/-)小鼠肾皮质中STAT3并没有被激活,而且p38的激活也受到抑制。结论熊果酸能减缓1型糖尿病小鼠肾脏的早期病变,其作用机制可能是因为熊果酸可以下调糖尿病引起的肾皮质中STAT3、ERK1/2和JNK的激活和i NOS的过量表达;STAT3、ERK1/2、JNK和p38通路在不同的糖尿病肾脏病变小鼠模型中的变化存在差异。
[Abstract]:Objective to study the effect of ursolic acid on streptozotocin (STZ). Effect and mechanism of renal lesion induced by STZ in type 1 diabetic mice. Methods male C57BL / 6 mice were randomly divided into diabetic group and non-diabetic group. Type 1 diabetes was induced by STZ. Equal volume 0.1 in mice. Mol/L citric acid solution was injected intraperitoneally 7 days after intraperitoneal injection of STZ. The diabetic mice were randomly divided into two groups: the control group and the control group. The mice in the group treated with ursolic acid and powdered animal food were mixed with ursolic acid according to 0.01 (drug / food quality). Male C57BL / 6 mice were randomly divided into two groups: one group was fed with low fat food. The other group was fed with high-fat food for 20 weeks. To measure glucose tolerance and insulin tolerance, male mice with C57BL / 6 background were divided into two groups: the first group was type 2 diabetes induced by gene mutation. One group of normal mice with the same age C57BL / 6 background was killed at the age of 12 weeks. The changes of messenger RNA levels of various genes related to pathological changes in renal cortex of diabetic mice were detected. The changes of these signaling pathways in the renal cortex of obese mice and dbher-r-mice fed with high-fat food were measured. Results 0.01%% ursolic acid was fed to type 1 diabetic mice for 12 weeks. It can significantly reduce the accumulation of type IV collagen in glomeruli and decrease glomerular swelling caused by diabetes, compared with non-diabetic mice. The levels of laminin 伪 -MCP-1 messenger RNA in diabetic mice were significantly increased. However, there was no effect on the elevated levels of laminin 伪 and MCP-1 messenger RNA in diabetic mice fed ursolic acid, similar to that in type 1 diabetic mice induced by STZ. STAT3 ERK1 / 2 and JNK were also activated in the renal cortex of obese mice fed with high fat. However, STAT3 was not activated and p38 activation was inhibited in the renal cortex of mice. Conclusion ursolic acid can attenuate the early renal lesion in type 1 diabetic mice. The mechanism may be that ursolic acid can down-regulate the activation of STAT3ERK1 / 2 and JNK and the overexpression of I NOS in renal cortex induced by diabetes. The changes of STAT3 ERK1 / 2 JNK and p38 pathways in different diabetic nephropathy mice were different.
【作者单位】：贵州省人民医院内分泌科;贵州省人民医院肾内科;贵州省人民医院内科;
【分类号】：R587.2;R692.9
【正文快照】： 熊果酸(ursolic acid)是存在于天然植物中的一种五环三萜类化合物,以游离形式或与糖结合成苷的形式分布于约7个科46个属62种植物中[1]。熊果酸作为一种中药成分,具有多种生物活性,在抗癌、防癌、保肝、抗菌、抗病毒、抗氧化等方面均有一定的作用。目前研究发现熊果酸的作用靶

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