邓老御膅膏对2型糖尿病大鼠的影响

Effect of TCM Master DENG Tietao's Yu Tang Soft Extract on Rats with Type 2 Diabetic Mellitus

目的观察邓老御膅膏(玉米须、黄精、茯苓、山药等)对2型糖尿病大鼠的影响。方法将SD大鼠随机分为正常组、模型组、消渴丸组(阳性对照药,0.78 g·kg^(-1))及邓老御膅膏低、中、高剂量组(5.63、11.25、22.50 g·kg^(-1)),每组12只。采用高脂饮食联合一次性腹腔注射链脲佐菌素(STZ,30 mg·kg^(-1))制备2型糖尿病大鼠模型。造模成功后灌胃给药,每天1次,连续8周。每周记录各组大鼠24 h平均饮水量;给药第2、4、6、8周检测大鼠空腹血糖(FBG);进行糖耐量(OGTT)试验,测定灌服葡萄糖后0、0.5、1、2 h的血糖值,计算时间-血糖曲线下面积(AUC);采用ELISA法测定血清胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR)与胰岛素敏感性指数(IAI);采用ELISA法测定全血糖化血红蛋白(HbA1c)及血清胰岛素样生长因子1(IGF-1)、C肽(C-P)水平;采用全自动生化分析仪测定血清总胆固醇(TCHO)、甘油三酯(TG)水平;苏木精-伊红(HE)染色观察大鼠胰腺组织病理变化,进行胰腺组织病理学半定量评分。结果与正常组比较,模型组大鼠出现多饮、多食、多尿现象,反应迟钝,第1~8周的饮水量均显著升高(P<0.01);给药第2~8周期间的FBG水平显著升高(P<0.01);口服葡萄糖后不同时间点的血糖水平及AUC值显著升高(P<0.01);血液中的HbA1c含量显著升高(P<0.01);各组大鼠的血清FINS含量无明显差异(P>0.05),模型组大鼠的HOMA-IR显著升高(P<0.01),IAI显著降低(P<0.01);血清IGF-1水平明显降低(P<0.05),C-P、TCHO、TG水平显著升高(P<0.05,P<0.01);胰岛腺泡形态不规则,体积缩小,腺泡细胞核增多,胰岛数量减少,部分胰岛见少量空泡变和胰腺淋巴细胞局灶性浸润,胰腺组织病理评分显著升高(P<0.01)。与模型组大鼠比较,邓老御膅膏给药组大鼠“三多一少”症状及精神状态得到一定改善,第1~7的周饮水量有不同程度降低(P<0.05,P<0.01);给药第2~8周期间的FBG水平有不同程度降低(P<0.05,P<0.01);口服葡萄糖后不同时间点的血糖水平及AUC值有一定程度降低,但差异无统计学意义(P>0.05);血液中的HbA1c含量显著降低(P<0.01);HOMA-IR有一定程度降低,但差异无统计学意义(P>0.05);血清C-P、TG水平明显降低(P<0.05,P<0.01),IGF-1水平有升高趋势,但差异无统计学意义(P>0.05);TCHO水平有下降趋势,但差异无统计学意义(P>0.05);胰岛腺泡形态不规则情况有所改善,胰岛数量有所增加,胰岛空泡变和淋巴细胞浸润减少,胰腺组织病理评分显著降低(P<0.01)。结论邓老御膅膏对2型糖尿病大鼠具有一定降糖作用,可能与其调节脂质代谢、修复胰岛损伤有关。

Objective To observe the effects of TCM Master DENG Tietao's Yu Tang Soft Extract(composed of corn stigma,Polygonati Rhizoma,Poria,Dioscoreae Rhizoma,etc.)on rats with type 2 diabetes mellitus(T2DM).Methods The SD rats were randomly divided into the normal group,the model group,the Xiaoke Pills group(positive control drug,0.78 g·kg^(-1))and Master DENG Tietao's Yu Tang Soft Extract low-,medium-and highdose groups(5.63,11.25 and 22.50 g·kg^(-1)respectively),with 12 rats in each group.The rat model of T2DM was prepared using a high-fat diet for 8 weeks combined with a single intraperitoneal injection of streptozotocin(STZ,30 mg·kg^(-1)).After successful modeling,the drug was administered by gavage once a day for 8 consecutive weeks.Fasting blood glucose(FBG)was measured at the second,fourth,sixth and eighth weeks of administration,and oral glucose tolerance test(OGTT)was measured at 0,0.5,1 and 2 hours after glucose administration,and the time of area under the curve(AUC)was calculated;the fasting insulin(FINS)was measured by ELISA and the homeostasis model assessment of insulin resistance index(HOMA-IR)and insulin sensitivity index(IAI)were calculated;the levels of total glycosylated haemoglobin(HbA1c)and serum insulin-like growth factor 1(IGF-1)and C-peptide(C-P)were measured by ELISA;the serum total cholesterol(TCHO)and triglyceride(TG)levels were measured by automatic biochemical analyzer;the histopathological changes of rat pancreas were observed by hematoxylin-eosin(HE)staining and the semi-quantitative score of pancreatic histopathology was performed.Results Compared with the normal group,the rats in the model group showed excessive drinking,eating,urinating and unresponsive,with significantly higher water consumption from week 1 to 8(P<0.01);the level of FBG was significantly increased from week 2 to 8 after administration(P<0.01);the blood glucose level and AUC value were significantly increased at different time points after oral glucose(P<0.01).Blood HbA1c content was significantly increased(P<0.01);there was no significant difference in serum FINS levels between the groups(P>0.05),HOMA-IR was significantly increased(P<0.01)and IAI was significantly decreased(P<0.01)in the model group;serum IGF-1 level was significantly decreased(P<0.05)and C-P,TCHO and TG levels were significantly increased(P<0.05,P<0.01);the pancreatic alveoli were irregular in shape,reduced in size,increased in the number of nuclei and pancreatic islets,and some pancreatic islets showed a small amount of vacuolation and focal infiltration of pancreatic lymphocytes,and the histopathological score of the pancreas was significantly increased(P<0.01).Compared with the rats in the model group,the rats in the Master DENG Tietao's Yu Tang Soft Extract administration groups showed some improvement in the symptoms of“polydipsia,polyuria,hypereating and weight loss”and mental status,and the weekly water intake from the week 1 to 7 decreased to different degrees(P<0.05,P<0.01);the FBG level from the week 2 to 8 of administration decreased to different degrees(P<0.05,P<0.01);blood glucose levels and AUC values at different time points after oral glucose administration decreased to some extent,but the difference was not statistically significant(P>0.05);HbA1c levels in blood were significantly decreased(P<0.01);HOMA-IR decreased to some extent,but the difference was not statistically significant(P<0.05);serum C-P and TG levels were significantly decreased(P<0.05,P<0.01),IGF-1 levels tended to increase,but the difference was not statistically significant(P>0.05);TCHO levels tended to decrease,but the difference was not statistically significant(P<0.05);irregularities in islet vesicle morphology were improved,the number of islets was increased,islet vacuolation and lymphocytic infiltration were decreased,and the histopathological score of the pancreas was significantly decreased(P<0.01).Conclusion Master DENG Tietao's Yu Tang Soft Extract has certain hypoglycemic effect on T2DM rats,which may be related to the regulation of lipid metabolism and repair of pancreatic islet damage.