生化汤对产后气虚血瘀大鼠静脉血栓栓塞症的防治机制研究_何珏.pdf

生化汤对产后气虚血瘀大鼠静脉血栓栓塞症的防治机制研究何珏1，郝小白1，张燕1，徐妍1，李虹1，盖云1，娄玉1，朱怡2(1 上海中医药大学附属第七人民医院，上海 200137;2 上海和睦家新城医院，上海201206)摘要 目的观察生化汤对产后气虚血瘀大鼠静脉血栓栓塞的防治效果，并从细胞因子角度探讨其作用机制。方法取产后雌鼠 20 只，随机选择 5 只作为正常组，余大鼠以力竭游泳方法复制产后气虚血瘀模型。将造模成功大鼠随机分为模型组、生化汤中剂量组、生化汤高剂量组，每组5 只。正常组和模型组给予蒸馏水灌胃，生化汤中、高剂量组分别给予含生药13 5 g/(kgd)和2025 g/(kgd)的生化汤药液灌胃，均 1 次/d，连续灌胃 14 d。灌胃第 14 天，于当天灌胃前对各组大鼠进行舌象观察并拍照，采用非临床研究组织病理图像数据自动定量分析管理系统对舌象图像进行分析，测定舌乳头密度、菌状乳头密度、顶端舌苔厚度和底端舌苔厚度。末次灌胃 30 min后，于各组大鼠背部皮下注射 0 8 mL/kg 盐酸肾上腺素，注射后立刻腹腔静脉采血，检测肿瘤坏死因子 (TNF )、血管内皮生长因子(VEGF)、细胞间黏附分子 1(ICAM 1)和 D 二聚体水平;处死各组大鼠，收集子宫进行 HE 染色观察。结果模型组大鼠舌色绛色，舌苔厚白，舌质湿腻，舌乳头密度和菌状乳头密度均明显低于正常组(P 均 0 05)，顶端舌苔和底端舌苔厚度均明显厚于正常组(P 均 0 05);生化汤中、高剂量组大鼠舌色淡红，舌苔少，舌质细嫩，舌乳头密度和菌状乳头密度均明显高于模型组(P 均 005)，顶端舌苔和底端舌苔厚度均明显薄于模型组(P 均 0.05)。模型组大鼠血清 TNF 、VEGF、ICAM 1 和 D 二聚体水平均明显高于正常组(P 均 0 05);生化汤中、高剂量组大鼠血清 TNF 、VEGF、ICAM 1 和 D 二聚体水平均明显低于模型组(P 均 0 05)，且生化汤高剂量组均明显低于生化汤中剂量组(P 均 0 05)。HE 染色显示，模型组大鼠子宫组织见静脉血栓栓塞，生化汤中、高剂量组大鼠无明显静脉血栓形成。结论生化汤可通过降低产后气虚血瘀大鼠血清 TNF 、VEGF、ICAM 1、D 二聚体水平而发挥抗炎、抗凝作用，可改善产后大鼠气虚血瘀本质，防治静脉血栓栓塞症。关键词生化汤;静脉血栓栓塞;气虚血瘀;肿瘤坏死因子 ;血管内皮生长因子;细胞间黏附因子 1;D 二聚体doi:10 3969/j issn 1008 8849 2022 22 007 中图分类号 332 文献标识码 A 文章编号 1008 8849(2022)22 3100 06 作者简介 何珏，女，博士，主治医师，研究方向为中医胎产病的预防与治疗。通信作者 朱怡，E mail:zhuyiwangyuxuan163 com 基金项目 上海中医药大学预算内项目(2020LK077);基于专病基础上治未病学科建设模式探索(PDZY 2019 0402);上海市第七人民医院“北斗星”人才培养(BDX2022 03)Preventive and therapeutic mechanism of Shenghua Decoction on venous thromboembolismin postpartum rats with Qi deficiency and blood stasisHE Jue1，HAO Xiaobai1，ZHANG Yan1，XU Yan1，LI Hong1，GE Yun1，LOU Yu1，ZHU Yi2(1 The Seventh People s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 200137，China;2 Shanghai United Family Xincheng Hospital，Shanghai 201206，China)Abstract:Objective It is to observe the preventive and therapeutic effects of Shenghua Decoction on venous thrombo-embolism in postpartum rats with Qi deficiency and blood stasis，and to explore its mechanism from the perspective of cyto-kines Methods Twenty postpartum female rats were selected，in which 5 rats were randomly selected as the normal group，0013现代中西医结合杂志 Modern Journal of Integrated Traditional Chinese and Western Medicine 2022 Nov，31(22)the rest rats were used to replicate the model of postpartum Qi deficiency and blood stasis by exhaustive swimming Thesuccessful modeled rats were randomly divided into model group，medium dose group of Shenghua Decoction and high dosegroup of Shenghua Decoction，with 5 rats in each group The normal group and the model group were given distilled waterby gavage，and the medium and high dose groups of Shenghua Decoction were given Shenghua Decoction containing 13 5g/(kgd)and 20 25 g/(kgd)of crude drugs respectively，once a day，for 14 days On the 14 th day of gavage，thetongue images of rats in each group were observed and photographed before gavage on the same day The tongue image ima-ges were analyzed using the non-clinical research automatic quantitative analysis management system of histopathological im-age data，and the density of tongue papilla，the density of fungiform papilla，the thickness of top tongue coating and bottomtongue coating were measured 30 min after the last intragastric administration，0 8 mL/kg adrenaline hydrochloride wasinjected subcutaneously into the back of rats in each group，and their blood was collected from abdominal vein immediatelyafter injection to detect the levels of tumor necrosis factor-(TNF-)，vascular endothelial growth factor(VEGF)，inter-cellular adhesion molecule-1(ICAM-1)and D-dimer;The rats in each group were killed and their uterus was collected forHE staining observation esults In the model group，the tongue color of rats was red，the tongue coating was thick andwhite，the tongue texture was wet and greasy，the density of tongue papilla and fungiform papilla were significantly lowerthan those in the normal group(all P 0 05)，and the thickness of the top and bottom tongue coating were significantlythicker than those in the normal group(all P 0 05);The tongue color of rats in the medium and high dose groups ofShenghua decoction was light red，the tongue coating was less，the tongue texture was delicate，the density of tongue papil-la and fungiform papilla were significantly higher than those in the model group(all P 0 05)，and the thickness of thetop and bottom tongue coating were significantly thinner than those in the model group(all P 0 05)The levels of serumTNF-，VEGF，ICAM-1 and D-dimer of rats in the model group were significantly higher than those in the normal group(all P 0 05);The levels of serum TNF-，VEGF，ICAM-1 and D-dimer of rats in the middle and high dose groups ofShenghua Decoction group were significantly lower than those of the model group(all P 0 05)，and the high dose groupof Shenghua Decoction was significantly lower than the middle dose group(P 0 05)HE staining showed that there wasvenous thromboembolism in the uterine tissue of rats in the model group，and there was no obvious venous thrombosis in themiddle and high dose groups of Shenghua Decoction Conclusion She