白芍总苷联合顺铂对胃癌模型大鼠的肿瘤抑制及肾损伤的改善作用
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篇名: 白芍总苷联合顺铂对胃癌模型大鼠的肿瘤抑制及肾损伤的改善作用
TITLE: Effects of Total Glucosides of Paeonia lactiflora Combined with Cisplatin on Tumor Inhibition and Renal Injury Improvement in Model Rats with Gastric Cancer
摘要: 目的:研究白芍总苷联合顺铂对胃癌模型大鼠的肿瘤抑制及对顺铂致肾损伤的改善作用。方法:将75只大鼠分为对照组(生理盐水,灌胃)、模型组(生理盐水,灌胃)、顺铂组(25mg/kg,腹腔注射)、白芍总苷组(200mg/kg,灌胃)、白芍总苷+顺铂组(灌胃200mg/kg白芍总苷+腹腔注射25mg/kg顺铂),每组15只。除对照组外,其余各组大鼠皮下接种胃癌BGC823细胞悬液复制胃癌模型。造模完成后,大鼠腹腔注射/灌胃给予相应药物,连续给药28d。测定大鼠瘤质量并计算肿瘤抑制率;采用流式细胞术检测大鼠肿瘤组织细胞凋亡率;采用Westernblotting法检测大鼠肿瘤组织中B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关的X蛋白(Bax)水平;采用酶联免疫吸附法或生化分析仪测定大鼠尿液中白细胞介素18(IL-18)和肾损伤分子1(KIM-1)水平,血清中尿素氮(BUN)和血肌酐(Scr)水平,以及肾组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)水平;采用苏木精-伊红染色法检测大鼠肾组织的病理学变化。结果:与对照组比较,模型组、白芍总苷组、白芍总苷+顺铂组大鼠尿液中IL-18、KIM-1水平,血清中BUN、Scr水平以及肾组织中SOD、MDA、GSH水平差异均无统计学意义(P>0.05);肾组织未见明显病理变化。与模型组比较,顺铂组大鼠瘤质量显著降低,细胞凋亡率显著升高,瘤组织中Bax蛋白表达水平显著升高、Bcl-2蛋白表达水平显著降低(P<0.05);尿液中IL-18、KIM-1水平,血清中BUN、Scr水平以及肾组织中MDA水平均显著升高(P<0.05);肾组织中SOD、GSH水平显著降低(P<0.05);肾组织出现肾小管扩张,并形成基底层上皮细胞空泡及肾小管内铸。与顺铂组比较,白芍总苷+顺铂组大鼠瘤质量显著降低,细胞凋亡率显著升高,瘤组织中Bax水平显著升高、Bcl-2水平显著降低(P<0.05);尿液中IL-18、KIM-1水平,血清中BUN、Scr水平以及肾组织中MDA水平均显著降低(P<0.05);肾组织中SOD、GSH水平显著升高;肾组织无肾小管扩张,偶见基底层上皮细胞空泡形成,少见肾小管内铸形成。与白芍总苷组比较,白芍总苷+顺铂组大鼠瘤质量显著降低,肿瘤抑制率显著升高,细胞凋亡率显著升高,瘤组织中Bax水平显著升高、Bcl-2水平显著降低(P<0.05);尿液中IL-18、KIM-1水平,血清中BUN、Scr水平以及肾组织中SOD、MDA、GSH水平差异均无统计学意义(P>0.05);肾组织偶见少量炎症细胞浸润。结论:白芍总苷联合顺铂能抑制胃癌大鼠肿瘤增长,促进肿瘤细胞凋亡,并可改善顺铂引起的肾功能损伤。
ABSTRACT: OBJECTIVE:To study the improvement effects of total glucosides of Paeonia l actiflora(TGPL)combined with cisplatin on tumor inhibition and renal injury in gastric cancer model rats. METHODS :Totally 75 rats were divided into control group(normal saline ,i.g.),model group (normal saline ,i.g.),cisplatin group (25 mg/kg,i.p.),TGPL group (200 mg/kg,i.g.), TGPL+cisplatin group (200 mg/kg TGPL ,i.g.+25 mg/kg cisplatin ,i.p.),with 15 rats in each group. Except for control group , gastric cancer rat models were established in other groups by subcutaneous inoculation of gastric cancer BGC 823 cell suspension. After modeling ,they were given relevant medicine intraperitoneally/intragastrically ,for consecutive 28 d. The tumor weight and tumor inhibition rate were measured. The apoptosis rate in tumor tissue was detected by flow cytometry ;Western blotting assay was used to detect the levels of Bcl- 2 and Bax in tumor tissue ;ELISA or biochemical analyzer were used to determine the levels of IL-18 and KIM- 1 in urine ,BUN and Scr in serum ,as well as SOD, MDA and GSH in renal tissue ; histopathological 015)changes of renal tissue in rats were detected by HE staining. 65896961。E-mail:taolitianxia999@163.com RESULTS: Compared with control group , there was no statistical significance in the levels of IL- 18 and KIM- 1 in urine,serum levels of BUN and Scr ,the levels of SOD MDA and GSH in renal tissue of model group (P>0.05);no obvious histopathological change was found in renal tissue. Compared with model group ,tumor weight in cisplatin group was decreased significantly ,while cell apoptosis was increased significantly,while expression level of Bax in tumor tissue was increased significantly ,the expression level of Bcl- 2 was decreased significantly(P<0.05);the levels of IL- 18 and KIM- 1 in urine ,BUN and Scr in serum and MDA in kidney were increased significantly(P<0.05);the levels of SOD and GSH in renal tissue were decreased significantly (P<0.05);renal tubules were dilated,vacuoles of epithelial cells in basal layer and cast in renal tubules formed . Compared with cisplatin ,tumor weight in TGPL+cisplatin group was decreased significantly ,while apoptotic rate was increased significantly ,while the level of Bax was increased significantly ,expression level of Bcl- 2 was decreased significantly (P<0.05);the levels of IL- 18 and KIM- 1 in urine , BUN and Scr in serum and MDA in renal tissue were significantly reduced (P<0.05);the levels of SOD and GSH in renal tissue were increased significantly (P<0.05);there was no tubule dilation ,but vacuoles were occasionally found in basal epithelial cells,and the cast formation in renal tubules was rare. Compared with TGPL group,tumor weight in TGPL +cisplatin group was significantly reduced ,the tumor inhibition rate was significantly increased ,the apoptosis rate was significantly increased ,while the expression level of Bax in tumor tissue was increased significantly ,expression level of Bcl- 2 was decreased significantly (P< 0.05);there was no statistical significance in the levels of IL- 18 and KIM- 1 in urine ,the levels of BUN and Scr in serum ,the levels of SOD ,MDA and GSH in renal tissue (P>0.05);a small amount of inflammatory cells infiltrated occasionally in renal tissue. CONCLUSIONS :TGPL combined with cisplatin can inhibit tumor growth ,promote tumor cell apoptosis and improve renal injury induced by cisplatin.
期刊: 2020年第31卷第13期
作者: 胡波,徐颖,朱琰琰
AUTHORS: HU Bo,XU Ying,ZHU Yanyan
关键字: 白芍总苷;顺铂;胃癌;肿瘤抑制;肾损伤;大鼠
KEYWORDS: Total glucosides of Paeonia lactiflora ;Cisplatin;Gastric cancer ;Tumor inhibition ;Renal injury ;Rat
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