No-1886对实验性糖尿病小型猪血糖、血脂异常和肝脏病变的保护作用观察

Observation of Protection Effect of No-1886 on Abnormal Blood Glucose,Blood Fat and Liver Pathological Changes in Miniature Pigs with Experimental Diabetes

目的 探讨合成化合物No 1886是否降低高糖高脂饲料诱发的糖尿病贵州小型猪的血浆葡萄糖、自由脂肪酸浓度和改善肝脏病变。方法 3～ 4月龄贵州小型猪 15只 (♂ 8只、♀ 7只 ) ,随机选取 5只饲以基础饲料为A组 (正常对照组 ) ;5只饲以高糖高脂饲料为B组 (糖尿病对照组 ) ;5只前 3个月饲以高糖高脂饲料 ,后 5个月饲以高糖高脂饲料加 1.0 %No 1886为C组 (糖尿病治疗组 ) ,分别在 0、2、3、4、5、6、8个月时从禁食过夜的猪眶静脉窦取血样测定葡萄糖、自由脂肪酸 ,第 8个月末 ,处死动物 ,取肝脏 1小块 ,10 %甲醛液固定 ,常规石蜡包埋切片 ,分别作HE和肝糖原染色以及油红O染色 ,光学显微镜下观察并照相。结果 糖尿病对照组和糖尿病治疗组加药前出现高血糖、高自由脂肪酸 ,并随着喂养时间的延长而逐渐升高。正常对照组血糖、自由脂肪酸未见明显升高 ,两组对比差异具有显著意义 (P <0 .0 5 ) ,与糖尿病对照组比较 ,糖尿病治疗组血糖、自由脂肪酸明显降低。从肝脏病理切片观察所见 ,糖尿病对照组肝脏肝细胞索排列紊乱 ,中央静脉扩张 ,肝细胞脂肪变性明显 ,具大量脂肪空泡 ,并有局灶溶解性坏死 ,淋巴细胞浸润 ,肝糖原极少或消失 ,油红O染色显示细胞内有较多脂滴。而糖尿病治疗组未见明显脂肪空泡变性 。

Objective To question whether No-1886, a synthetic compound, decreases plasma glucose and free fatty acids or improves pathological changes in diabetic Guizhou Minipigs induced by high sucrose and high fat feed. Methods 15 Guizhou Minipigs about 3-4 months were randomly divided into 3 groups of normal control, diabetes, diabetes treatment, which were fed by basal diet,high sucrose and high fat feed or with 1.0% No-1886 respectively.The concentration of plasma glucose and free fatty acids of minipigs,which were fasting the previous night,were analyzed in the 0,2,3,4,5,6,8th month respectively.These minipigs were put to death at the end of 8th month, liver pathologic changes were observed under microscope after the small lumps of liver were fixed with formalin and stained with Oil Red O or liver glycogen (PAS). Results The high plasma glucose and free fatty acids were observed one month late and gradually increased in the diabetes group but not in normal control group(P<0.05).The plasma glucose and free fatty acids of diabetes treatment group were lower than those in diabetes control group. The normal liver structure and abundant glycogen were observed in the treatment group. There were obvious liver fatty degeneration, many fat bubbles, local soluble necrosis, infiltration of a few lymphocytes and little or no glycogen in diabetes group. Conclusion No-1886 improved lipid metabolic disorder and liver fat pathological changes,and decreased plasma glucose or liver glycogenolysis.No-1886 may be developed as an agent to treat glucose metabolic disorder or lipid disorder in diabetes.