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1.河北中医学院,石家庄 050091
2.络病研究与创新中药国家重点实验室,石家庄 050035
3.河北省络病重点实验室,石家庄 050035
4.河北医科大学,石家庄 050017
5.国家中医药管理局重点研究室(心脑血管络病),石家庄 050035
Received:13 December 2021,
Published Online:02 March 2022,
Published:20 April 2022
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张少兰,侯云龙,马坤等.津力达颗粒对糖尿病前期大鼠内脏脂肪蓄积的影响[J].中国实验方剂学杂志,2022,28(08):37-45.
ZHANG Shao-lan,HOU Yun-long,MA Kun,et al.Effect of Jinlida Granules on Visceral Fat Accumulation in Prediabetic Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(08):37-45.
张少兰,侯云龙,马坤等.津力达颗粒对糖尿病前期大鼠内脏脂肪蓄积的影响[J].中国实验方剂学杂志,2022,28(08):37-45. DOI: 10.13422/j.cnki.syfjx.20220839.
ZHANG Shao-lan,HOU Yun-long,MA Kun,et al.Effect of Jinlida Granules on Visceral Fat Accumulation in Prediabetic Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(08):37-45. DOI: 10.13422/j.cnki.syfjx.20220839.
目的
2
研究津力达颗粒对糖尿病前期大鼠内脏脂肪蓄积及其引起的炎症反应的影响。
方法
2
将SD大鼠随机分为正常组、模型组、津力达低剂量组(1.5 g·kg
-1
)、津力达高剂量组(3.0 g·kg
-1
)和阿托伐他汀组(10 mg·kg
-1
)。采用高糖高脂联合小剂量链脲佐菌素(STZ)少量多次腹腔注射法建立糖尿病前期大鼠模型,造模8周后,给药干预13周。测定大鼠体质量、口服葡萄糖耐量(OGTT)、空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)。微型计算机断层成像技术(Micro-CT)观测内脏脂肪含量。苏木素-伊红(HE)染色观察脂肪组织病理变化。酶联免疫吸附测定法(ELISA)检测大鼠肿瘤坏死因子-
α
(TNF-
α
)和白细胞介素-6(IL-6)含量。免疫荧光法和蛋白免疫印迹法(Western blot)检测内脏脂肪中巨噬细胞标记物CD68表达情况。
结果
2
与正常组比较,模型组大鼠OGTT、FBG、FINS、HOMA-IR、TC、LDL-C显著升高(
P
<
0.01),HDL-C显著降低(
P
<
0.01),体质量与内脏脂肪含量明显增加(
P
<
0.05,
P
<
0.01),脂肪细胞异常肥大,CD68蛋白表达和TNF-
α
、IL-6含量显著升高(
P
<
0.01);与模型组比较,津力达各剂量组能够降低糖尿病前期大鼠OGTT、HOMA-IR、TC和LDL-C水平(
P
<
0.05,
P
<
0.01),减轻糖尿病前期大鼠体质量和内脏脂肪含量(
P
<
0.05),减小脂肪细胞肥大,减少CD68蛋白表达和TNF-
α
、IL-6的含量(
P
<
0.05,
P
<
0.01)。
结论
2
津力达可以通过减少糖尿病前期大鼠的内脏脂肪蓄积及其引起的炎症反应,从而改善糖尿病前期大鼠的胰岛素抵抗,为津力达颗粒在糖尿病前期的临床治疗中提供新的药理依据。
Objective
2
To study the effect of Jinlida granules on visceral fat accumulation and its induced inflammatory response in prediabetic rats.
Method
2
Male SD rats were randomly divided into normal group, model group, Jinlida low-dose group (1.5 g·kg
-1
), Jinlida high-dose group (3.0 g·kg
-1
) and atorvastatin group (10 mg·kg
-1
). Prediabetic rat model was established using high-carbohydrate, high-fat diet combined with low-dose streptozotocin (STZ) by multiple small-dose intraperitoneal injections. After 8 weeks of modeling and drug intervention for 13 consecutive weeks, body weight, oral glucose tolerance test(OGTT), fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (HOMA-IR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured in each group of rats. The content of visceral fat was quantified by micro-computed tomography (Micro-CT). Hematoxylin-eosin staining (HE) was used to observe the pathological changes of fat cells. The levels of tumor necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) in rat visceral fat and serum were determined by enzyme linked immunosorbent assay (ELISA). The expression of macrophage marker CD68 in visceral fat was detected by immunofluorescence and Western blot.
Result
2
Compared with normal group, model group had increased oral glucose tolerance, FBG, FINS, HOMA-IR, TC, LDL-C (
P
<
0.01), elevated body weight and visceral fat accumulation (
P
<
0.05,
P
<
0.01), enhanced CD68 protein expression and TNF-
α
and IL-6 levels (
P
<
0.01), decreased HDL-C (
P
<
0.01), and abnormal hypertrophy of adipocytes. Compared with model group, Jinlida high- and low-dose groups lowered oral glucose tolerance, HOMA-IR, TC and LDL-C (
P
<
0.05,
P
<
0.01), body weight and visceral fat accumulation (
P
<
0.05), and CD68 protein expression and TNF-
α
and IL-6 levels (
P
<
0.05,
P
<
0.01) and lessened hypertrophy of fat cells.
Conclusion
2
Jinlida can improve the insulin resistance in prediabetic rats by reducing visceral fat accumulation and its induced inflammatory response, which provides a new pharmacological basis for clinical treatment of prediabetes by Jinlida granules.
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