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上海中医药大学附属龙华医院,上海中医药大学龙华临床医学院(上海 200032)
Published:25 May 2024,
Received:14 November 2023,
Revised:02 January 2024,
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吴盼晴,丛超,刘希昱等.和坤汤对去卵巢大鼠阴道子宫形态学及肝肾功能的影响[J].上海中医药大学学报,2024,38(03):57-65.
WU Panqing,CONG Chao,LIU Xiyu,et al.Effects of Hekun Decoction on vagina and uterus morphology and liver and kidney functions in ovariectomized rats[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2024,38(03):57-65.
吴盼晴,丛超,刘希昱等.和坤汤对去卵巢大鼠阴道子宫形态学及肝肾功能的影响[J].上海中医药大学学报,2024,38(03):57-65. DOI: 10.16306/j.1008-861x.2024.03.009.
WU Panqing,CONG Chao,LIU Xiyu,et al.Effects of Hekun Decoction on vagina and uterus morphology and liver and kidney functions in ovariectomized rats[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2024,38(03):57-65. DOI: 10.16306/j.1008-861x.2024.03.009.
目的
2
探讨中药复方和坤汤对去卵巢大鼠阴道、子宫形态学的影响,并观察该方的肝、肾毒性。
方法
2
将40只雌性SD大鼠随机分为4组:对照组、模型组、雌二醇(E
2
)组、和坤汤组,每组10只。除对照组外,其余大鼠采用去势手术构建围绝经期模型。术后第10天,对照组和模型组大鼠每天给予0.9% NaCl溶液灌胃,E
2
组每天给予0.15 mg/kg E
2
溶液灌胃,和坤汤组每天给予19.95 g/kg和坤汤颗粒剂混悬液灌胃,连续3个月。干预结束后处死大鼠,摘取阴道、子宫、肝脏、肾脏,计算脏器指数;苏木素-伊红(HE)染色观察各组大鼠的阴道、子宫、肝脏、肾脏形态学变化,并测量大鼠的阴道上皮厚度、上皮层数、固有层血管数量及子宫上皮厚度、内膜厚度、内膜腺腺体上皮高度和内膜腺个数;采用免疫组化方法检测大鼠阴道雌激素受体α(ERα)和ERβ表达;采用全自动生化分析仪检测大鼠的肝肾功能指标,包括丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、超氧化物歧化酶(SOD)、血肌酐(Scr)、血尿素氮(BUN);采用酶联免疫吸附试验(ELISA)检测大鼠的血清E
2
水平。
结果
2
与模型组相比,E
2
组、和坤汤组大鼠的阴道指数显著上升(
P
<
0.01),阴道上皮厚度、阴道上皮层数、阴道固有层血管数量均显著增加(
P
<
0.01)。与模型组相比,E
2
组大鼠的子宫指数显著上升(
P
<
0.01),子宫上皮厚度、子宫内膜厚度、子宫内膜腺个数、子宫内膜腺腺体上皮高度均显著增加(
P
<
0.01,
P
<
0.05);和坤汤组大鼠的子宫指数显著上升(
P
<
0.05),子宫内膜厚度、子宫内膜腺腺体上皮高度显著增加(
P
<
0.01)。与模型组相比,E
2
组、和坤汤组大鼠的血清E
2
水平及阴道ERα、ERβ表达水平均显著升高(
P
<
0.01,
P
<
0.05)。与对照组相比,模型组、E
2
组及和坤汤组大鼠的肝脏、肾脏均未见明显病理损伤,且各组大鼠的肝肾功能指标水平比较,差异均无统计学意义(
P
>
0.05)。
结论
2
和坤汤能提高去卵巢大鼠的血清E
2
水平,增加阴道雌激素受体表达,改善阴道萎缩,且作用温和,对子宫刺激较小、对肝肾功能无毒性作用。
Objective: To investigate the effects of traditional Chinese medicine compound formula Hekun Decoction on the vaginal and uterine morphology of ovariectomized rats, and observe its liver and kidney toxicity.
Methods
2
Forty female SD rats were randomly divided into four groups: control group, model group, estradiol (E
2
) group, and Hekun Decoction group, 10 rats in each group. Except for the control group, the perimenopausal model was constructed by gonadectomy in other rats. On the 10th day after surgery, the rats in the control and model groups were given 0.9% NaCl solution by gavage every day, the rats in the E
2
group were given 0.15 mg/kg E
2
solution by gavage every day, and the rats in the Hekun Decoction group were given 19.95 g/kg Hekun Decoction granule solution by gavage every day, with a course of 3 consecutive months. The rats were executed at the end of the intervention, and the vagina, uterus, liver, and kidneys were removed and the organ indices were calculated. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of vagina, uterus, liver and kidney of rats in each group, and the thickness of the vaginal epithelium, the number of the vaginal epithelial layers, the number of blood vessels in the lamina propria of vagina, and the thickness of the uterine epithelium, the thickness of the endometria, the epithelium height of the endometria gland and the number of endometria glands were measured. The expressions of vaginal estrogen receptor α (ERα) and estrogen receptor β (ERβ) in rats were detected by immunohistochemical methods. The indicators of liver and kidney functions of rats, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), serum creatinine (Scr) and blood urea nitrogen (BUN), were detected by fully aut
omatic biochemical analyzer. The serum E
2
level of rats was detected by enzyme-linked immunosorbent assay (ELISA).
Results
2
Compared with the model group, the vaginal index of rats in the E
2
and Hekun Decoction groups was significantly increased (
P
<
0.01), and the thickness of the vaginal epithelium, the number of the vaginal epithelial layers, and the number of blood vessels in the lamina propria of vagina were significantly increased (
P
<
0.01). Compared with the model group, the uterine index of rats in the E
2
group was significantly increased (
P
<
0.01), and the thickness of the uterine epithelium, the thickness of the endometria, the number of endometria glands and the epithelium height of the endometria gland were significantly increased (
P
<
0.01,
P
<
0.05); the uterine index of rats in the Hekun Decoction group was significantly increased (
P
<
0.05), and the thickness of the endometria and the epithelium height of the endometria gland were significantly increased (
P
<
0.01). Compared with the model group, the serum E
2
level and the vaginal ERα and ERβ expression levels of rats in the E
2
and Hekun Decoction groups were significantly increased (
P
<
0.01,
P
<
0.05). Compared with the control group, there were no obvious pathological damages in the liver and kidney of rats of the model, E
2
and Hekun Decoction groups, and there were no statistically significant differences on the levels of liver and kidney function indexes of rats in all groups (
P
>
0.05).
Conclusion
2
Hekun Decoction can enhance the serum E
2
level of ovariectomized rats, increase the expressions of vaginal estrogen receptors, improve vaginal atrophy, and its action is mild, with less stimulation to the uterus and no toxic effect o
n the liver and kidney functions.
和坤汤围绝经期阴道萎缩雌二醇肝肾毒性去卵巢大鼠
Hekun Decoctionperimenopausevaginal atrophyestradiolliver and kidney toxicityovariectomized rat
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