| 引用本文:吕美豫1，张建军1，刘金莲1，侯新娟1，姜砚馨1，郑婷1，乐娜1，张宝旭2，贾凤兰2，周澜华3.肾虚血瘀证大鼠模型的建立及补肾活血方补肾益精活血化瘀功效研究[J].世界中医药,2024,(12):. |
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| 肾虚血瘀证大鼠模型的建立及补肾活血方补肾益精活血化瘀功效研究 |
| Establishment of a Rat Model with Syndrome of Kidney Deficiency and Blood Stasis and Characterization of Kidney-tonifying，Essence-and Blood Activating Effects of Bushen Huoxue Formula |
| 投稿时间：2024-04-10 |
| DOI：10.3969/j.issn.1673-7202.2024.12.006 |
| 中文关键词: 肾虚血瘀证 大鼠模型 方证相应 补肾活血方 功效 补肾益精 活血化瘀 卵巢功能 |
| English Keywords:Syndrome of kidney deficiency and blood stasis Rat model Correspondence between syndrome and formula Bushen Huoxue Formula Efficacy Tonifying kidney and replenishing essence Activating blood and resolving stasis Ovarian function |
| 基金项目:国家重点研发计划中医药现代化研究重点专项（2018YFC1706800） |
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| 中文摘要: |
| 目的：通过建立肾虚血瘀证大鼠模型并基于方证相应研究补肾活血方的补肾益精、活血化瘀功效。方法：将48只雌性SD大鼠随机分为正常对照组、模型组、阳性药组、补肾活血方低剂量组（0.72 g/kg）、补肾活血方中剂量组（1.44 g/kg）、补肾活血方高剂量组（2.89 g/kg），每组8只。除正常对照组外，各组从第1天开始，上午灌胃造模药羟基脲溶液（450 mg/kg），连续14 d，从第4天上午开始加用肾上腺素0.3 mg/(kg·d)皮下注射至第14天，制备大鼠肾虚血瘀模型。观察大鼠的一般状态，检测子宫和卵巢脏器指数、卵泡数目、黄体数量，血清雌二醇(E2)、卵泡刺激素(FSH)、抑制素B（INHB）、红细胞（RBC）、血红蛋白（HGB）、红细胞比容（HCT）、血栓素（TXB-2）、内皮素（ET-1）的水平，血浆红细胞压积、红细胞聚集指数、红细胞变形指数。结果：与正常对照组比较，模型组子宫指数和卵巢指数均下降（P<0.001），卵泡数目下降（P<0.05），黄体数目上升（P<0.05），血清E2、FSH含量均降低，INHB含量升高（P<0.001），RBC、HGB、HCT含量均降低（P<0.001），血浆红细胞压积、红细胞聚集指数、红细胞变形指数均升高（P<0.01，P<0.001），血清ET-1、TXB-2含量均升高（P<0.001）。与模型组比较，给药组卵巢指数均上升（P<0.01，P<0.001），而子宫指数除补肾活血方高剂量组，其他给药组均上升（P<0.05）；给药组卵泡数目均上升（P<0.05，P<0.01，P<0.001），补肾活血方各剂量组黄体数量降低（P<0.05）；给药组血清E2、FSH均升高（P<0.01，P<0.001）、INHB含量均降低（P<0.001），补肾活血方各剂量组RBC、HGB、HCT含量均升高，差异有统计学意义；给药组血清ET-1、TXB-2含量均降低（P<0.001），血浆红细胞压积和红细胞聚集指数均降低（P<0.001），红细胞变形指数除了补肾活血方高剂量组，其余给药组均降低（P<0.05）。结论：首次通过灌胃羟基脲结合皮下注射肾上腺素建立大鼠肾虚血瘀证模型，补肾活血方可以改善卵巢功能和激素水平，具有补肾益精、补血功效，且通过改变血液流变学的异常，改善内皮细胞功能，降低血栓素，从而达到活血化瘀之功。 |
| English Summary: |
| To establish a rat model with the syndrome of kidney deficiency and blood stasis and study the kidney-tonifying，essence-replenishing，blood-activating，and stasis-resolving effects of Bushen Huoxue Formula based on the correspondence between syndrome and formula.Methods:A total of 48 female SD rats were randomized into normal，model，positive drug，and low-(0.72 g/kg)，medium-(1.44 g/kg)，and high-dose(2.89 g/kg) Bushen Huoxue Formula groups(n=8).The rats in other groups except the normal group were administrated with hydroxyurea solution(450 mg/kg) by gavage from the morning of day 1 for 14 consecutive days.From the morning of day 4，epinephrine [0.3 mg/(kg·d)] was injected subcutaneously until day 14 for the modeling of kidney deficiency and blood stasis.The general state of the rats was observed，and the uterus and ovary indexes were calculated.Meanwhile，the number of follicles，number of corpus luteum，serum levels of estrodiol(E2)，follicle-stimulating hormone(FSH)，inhibin B(INHB)，red blood cells(RBC)，hemoglobin(HGB)，hematocrit(HCT)，thromboxane B2(TXB-2)，endothelin(ET-1)，plasma hematocrit，erythrocyte aggregation index，and erythrocyte deformity index were counted and determined.Results:Compared with the normal group，the model group showed decreased uterus index and ovary index(P<0.001)，reduced number of follicles(P<0.05)，increased number of corpus luteum(P<0.05)，lowered serum E2 and FSH levels，elevated INHB level(P<0.001)，declined RBC，HGB，and HCT levels(P<0.001)，increased HCT，erythrocyte aggregation index，and erythrocyte deformity index(P<0.01，P<0.001)，and risen serum ET-1 and TXB-2 levels(P<0.001).Compared with the model group，drug interventions increased the ovary index(P<0.01，P<0.001) and the uterus index(P<0.05，except the high-dose Bushen Huoxue Formula group).Drug interventions increased the number of follicles(P<0.05，P<0.01，P<0.001)，and Bushen Huoxue Formula decreased the number of corpus luteum(P<0.05).In addition，drug interventions elevated the serum E2 and FSH levels(P<0.01，P<0.001) and lowered the INHB level(P<0.001)，and Bushen Huoxue Formula at different doses increased the RBC，HGB，and HCT.Drug interventions lowered the serum levels of ET-1 and TXB-2(P<0.001) and decreased HCT(P<0.001)，erythrocyte aggregation index(P<0.001)，and erythrocyte deformation index(P<0.05，except the high-dose Bushen Huoxue Formula group).Conclusion:For the first time，the rat model with the syndrome of kidney deficiency and blood stasis was established by intragastric administration of hydroxyurea combined with subcutaneous injection of adrenaline.Bushen Huoxue Formula can improve the ovarian function and restore the hormone levels to exert the effects of tonifying kidney，replenishing essence，and tonifying blood.Moreover，it can improve the endothelial cell function and reduce thromboxane to active blood and resolve stasis by changing the rheological abnormalities of blood. |
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