黄芪甲苷对链脲佐菌素诱导糖尿病肾病大鼠的作用机制
Mechanism of Astragaloside IV on diabetic nephropathy induced by Streptozotocin in rats
- 北京中医药 2023年42卷第4期 页码：403-407
- 作者机构：
1.首都医科大学附属北京天坛医院中医针灸科，北京 100070
2.中日友好医院临床医学研究所，北京 100029
- 作者简介：
黄利霞，女，24岁，硕士研究生。研究方向：中西医结合临床医学。
范愈燕，E-mail：fanyy2002@hotmail.com
- 基金信息：国家自然科学基金资助项目(81774214)
DOI：10.16025/j.1674-1307.2023.04.014
中图分类号：纸质出版日期：2023-04-25，
收稿日期：2022-03-18，
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黄利霞，李忻，张舒，等.黄芪甲苷对链脲佐菌素诱导糖尿病肾病大鼠的作用机制［J］.北京中医药，2023，42（4）：403-407.
HUANG Li-xia,LI xin,ZHANG Shu,et al.Mechanism of Astragaloside IV on diabetic nephropathy induced by Streptozotocin in rats[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(04):403-407.
黄利霞，李忻，张舒，等.黄芪甲苷对链脲佐菌素诱导糖尿病肾病大鼠的作用机制［J］.北京中医药，2023，42（4）：403-407. DOI： 10.16025/j.1674-1307.2023.04.014.
HUANG Li-xia,LI xin,ZHANG Shu,et al.Mechanism of Astragaloside IV on diabetic nephropathy induced by Streptozotocin in rats[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(04):403-407. DOI： 10.16025/j.1674-1307.2023.04.014.
摘要
目的
2
探讨黄芪甲苷（AS-IV）对链脲佐菌素（STZ）诱导糖尿病肾病（DN）大鼠的作用机制。
方法
2
选择SPF级雄性6周龄SD大鼠30只，随机取6只大鼠作为对照组，剩余24只大鼠按65 mg/kg腹腔注射STZ（溶于0.1 mol／L柠檬酸缓冲液，pH 4.4）制备DN模型，对照组腹腔注射等体积0.1 mol/L柠檬酸缓冲液，将模型大鼠随机分为模型组、AS-IV组、胰岛素（INS）组、AS-IV+INS组各6只，分别给予AS-IV 10 mg/kg、INS 5 U、AS-IV 10 mg/kg+INS 5 U灌胃，对照组和模型组灌胃等体积1%羧甲基纤维素钠溶液，1次/d，干预8周。对比各组血糖、体质量、尿蛋白、BUN、Scr、HbA
1
c，血清和肾组织一氧化氮（NO）水平，肾组织中内皮型一氧化氮合酶（eNOS）、磷酸化一氧化氮合成酶丝氨酸1177位点［p-eNOS（Ser1177）］和苏氨酸495位点［p-eNOS（Thr495）］蛋白表达。
结果
2
与对照组比较，模型组血糖均升高（
P
<
0.05）；AS-IV组、INS组、AS-IV+INS组从第8周开始血糖值均低于模型组（
P
<
0.05）；但AS-IV组、INS组、AS-IV+INS组间血糖比较差异无统计学意义（
P>
0.05）。与对照组比较，所有造模大鼠体质量低（
P<
0.05），尿蛋白、BUN、Scr、HbA
1
c高（
P<
0.05）；与模型组比较，AS-IV组、INS组、AS-IV+INS组体质量高（
P<
0.05），尿蛋白、BUN、Scr、HbA
1
c低（
P<
0.05）；与INS组比较，AS-IV+INS组尿蛋白、Scr低（
P<
0.05）。与对照组比较，模型组血清和肾组织NO水平低（
P<
0.05）；与模型组比较，AS-IV组、INS组、AS-IV+INS组血清和肾组织NO水平高（
P<
0.05）；与INS组比较，AS-IV+INS组肾组织NO水平高（
P<
0.05）。与对照组比较，模型组肾组织中p-eNOS（Ser1177）蛋白表达低（
P<
0.01）；与模型组比较，AS-IV组、AS-IV+INS组肾组织中p-eNOS（Ser1177）蛋白表达高（
P<
0.01）。
结论
2
黄芪甲苷可能通过eNOS/NO通路对STZ诱导DN大鼠发挥治疗，且作用位点可能在Ser1177。
Abstract
Objective
2
To explore the protective mechanism of astragaloside Ⅳ （AS-IV） through endothelial nitric oxide synthase （eNOS）/nitric oxide（NO） pathway in kidney of diabetic rats.
Methods
2
Thirty SPF male SD rats aged 6 weeks were selected. Except of the control group（n=6）， the remaining 24 rats were intraperitoneally injected with 65 mg/kg STZ （dissolved in 0.1 mol/L citric acid buffer， pH 4.4） to make DN model， while the control group was intraperitoneally injected with the same volume of 0.1 mol/L citric acid buffer. The model rats were randomly divided into model group， AS-IV group， insulin （INS） group and AS-IV+INS group with 6 rats in each group. AS-IV 10 mg/kg， INS 5 U and AS-IV 10 mg/kg+INS 5 U were given by gavage respectively， and the control group and the model group were given the same volume of 1% sodium carboxymethyl cellulose solution once a day for 8 weeks. The blood sugar， body weight， urine protein， BUN， Scr， HbA
1
c， nitric oxide （NO） levels in serum and kidney， and the sites of endothelial nitric oxide synthase （eNOS）， phosphorylated nitric oxide synthase serine 1 177 ［P-Enos （SER 1 177）］ and threonine 495 ［P-Enos （THR 495）］ in kidney were compared.
Results
2
Compared with the control group， the blood sugar in the model group was increased （
P
<
0.05）. The blood sugar levels in As-ⅳ group， INS group and As-ⅳ+INS group were lower than those in the model group from the 8th week （
P
<
0.05）. However， there was no significant difference in blood glucose among As-ⅳ group， INS group and As-ⅳ+INS group （
P
>
0.05）. Compared with the control group， the body weight of the model group was lower （
P
<
0.05）， and the urine protein， BUN， Scr and HbA
1
c were higher （
P
<
0.05）. Compared with the model group， AS-IV group， INS group and AS-IV+INS group had higher body mass （
P
<
0.05）， but lower urine protein， BUN， Scr and HbA
1
c （
P
<
0.05）. Compared with INS group， urinary protein and Scr in AS-ⅳ+INS group were lower （
P
<
0.05）. Compared with the control group， the level of NO in serum and kidney tissue in the model group was lower （
P
<
0.05）. Compared with the model group， AS-IV group， INS group and AS-IV+INS group had higher levels of NO in serum and kidney tissue （
P
<
0.05）. Compared with INS group， the level of NO in renal tissue in AS-ⅳ+INS group was higher （
P
<
0.05）. Compared with the control group， the expression of p-eNOS（Ser1177） protein in renal tissue of model group was lower （
P
<
0.01）. Compared with the model group， the expression of p-eNOS（Ser1177） protein in renal tissue of As-ⅳ group and As-ⅳ+INS group was higher （
P
<
0.01）.
Conclusion
2
Astragaloside IV may play a role in treating STZ-induced DN rats through eNOS/NO pathway， and the site of action may be Ser1177.
关键词
糖尿病肾病黄芪甲苷eNOS/NO通路大鼠
Keywords
Diabetic nephropathyAS-IVeNOS/NO passwayrat
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