蒙药协日嘎-4对肾损伤模型大鼠的保护作用
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摘要
目的研究协日嘎-4对庆大霉素致急性肾损伤模型大鼠的保护作用。方法将健康雄性Wistar大鼠随机分为空白组、模型组、协日嘎-4低剂量组、协日嘎-4中剂量组、协日嘎-4高剂量组、肾炎消肿片组、强的松组,除空白组外,所有大鼠皮下注射庆大霉素[80 mg/(kg·d)]诱导急性肾损伤,连续6 d。造模结束2 h后分别给予相应药物治疗,连续给药14 d,给药结束后,用酶联免疫吸附法(ELISA)检测血清肌酐(Scr)、血清尿素氮(BUN)、尿蛋白(UP)、尿酶(NAG)、肾损伤因子(KIM-1)的表达水平。计算各组肾脏指数(KI)和前列腺指数(PI),用苏木素-伊红(HE)染色处理肾组织切片,光镜观察组织病理学改变。结果与空白组相比,模型组大鼠尿量增加(P<0.01),Scr、BUN、UP、NAG、KIM-1的含量均升高(P<0.01),KI、PI也有不同程度的升高(P<0.01)。与模型组相比,协日嘎-4低剂量组可较快的降低Scr、BUN、UP、PI的表达水平(P<0.01),持续用药至一定血药浓度可降低NAG、KIM-1的表达水平(P<0.01),协日嘎-4中、高剂量组可降低庆大霉素致肾损伤模型大鼠的尿量(P<0.05、P<0.01),降低Scr、BUN、UP、NAG、KIM-1、KI、PI的表达水平(P<0.05、P<0.01)。阳性对照药在疾病发生的一定时间段内可降低某些因子的表达水平,但在整个实验过程中,协日嘎-4治疗组要优于阳性对照组。协日嘎-4低、中、高剂量组肾小球系膜细胞增生改善、肾小管上皮细胞脱落现象明显得到抑制。结论协日嘎-4对庆大霉素致肾损伤模型大鼠有保护作用,并对肾损伤导致的PI增大有一定的治疗效果。
Objective To study the protective effect of Mongolian medicinal Xieri GA-4 in rat model of acute kidney injury induced by gentamicin. Methods Male healthy Wistar rats were randomly divided into blank group, model group, low-dose, mid-dose, high-dose Xieri GA-4 groups, group of Shenyan Xiaozhong Pian(Nephritis Swelling-relieving Tablet, SYXZ Tablet group) and prednison group. Except of blank group, other groups were given hypodermic injection of gentamicin(80 mg/kg·d) for reducing acute kidney injury for 6 d, and were treated with corresponding medicianls after 2 h for 14 d. The levels of serum creatinine(SCr), blood urea nitrogen(BUN), urine protein(UP), uracil-N-glycosylase(NAG) and kidney injury molecular(KIM-1) were detected by using ELISA after treatment. The kidney index(KI) and prostatic index(PI) were calculated in all groups. The histopathological changes of kidney tissue were observed with light microscope after HE staining. Results Compared with blank group, the urine volume(P<0.01), and levels of Scr, BUN, UP, NAG and KIM-1(P<0.01) increased, and expressions of KI and PI(P<0.01) also increased in model group. Compared with model group, the levels of Scr, BUN and UP and PI decreased quickly(P<0.01), and expressions of NAG and KIM-1 were reduced after medicinal reaching to certain dose after continuous administration in low-dose Xieri GA-4 group(P<0.01). The urine volume, and levels of Scr, BUN, UP, NAG and KIM-1(P<0.05, P<0.01), and expressions of KI and PI decreased in mid-dose and high-dose Xieri GA-4 groups(P<0.05, P<0.01). The levels of some factors decreased in prednison group and SYXZ Tablet group in a period, but the results were better in all Xieri GA-4 groups during the whole experimental course. The proliferation of mesangial cells was relieved and tubular desquamation was significantly inhibited in low-dose, mid-dose, high-dose Xieri GA-4 groups. Conclusion Xieri GA-4 has a protective effect on rat model of kidney injury induced by gentamicin, and has therapeutic effect on PI increase induced by kidney injury.
Objective To study the protective effect of Mongolian medicinal Xieri GA-4 in rat model of acute kidney injury induced by gentamicin. Methods Male healthy Wistar rats were randomly divided into blank group, model group, low-dose, mid-dose, high-dose Xieri GA-4 groups, group of Shenyan Xiaozhong Pian(Nephritis Swelling-relieving Tablet, SYXZ Tablet group) and prednison group. Except of blank group, other groups were given hypodermic injection of gentamicin(80 mg/kg·d) for reducing acute kidney injury for 6 d, and were treated with corresponding medicianls after 2 h for 14 d. The levels of serum creatinine(SCr), blood urea nitrogen(BUN), urine protein(UP), uracil-N-glycosylase(NAG) and kidney injury molecular(KIM-1) were detected by using ELISA after treatment. The kidney index(KI) and prostatic index(PI) were calculated in all groups. The histopathological changes of kidney tissue were observed with light microscope after HE staining. Results Compared with blank group, the urine volume(P<0.01), and levels of Scr, BUN, UP, NAG and KIM-1(P<0.01) increased, and expressions of KI and PI(P<0.01) also increased in model group. Compared with model group, the levels of Scr, BUN and UP and PI decreased quickly(P<0.01), and expressions of NAG and KIM-1 were reduced after medicinal reaching to certain dose after continuous administration in low-dose Xieri GA-4 group(P<0.01). The urine volume, and levels of Scr, BUN, UP, NAG and KIM-1(P<0.05, P<0.01), and expressions of KI and PI decreased in mid-dose and high-dose Xieri GA-4 groups(P<0.05, P<0.01). The levels of some factors decreased in prednison group and SYXZ Tablet group in a period, but the results were better in all Xieri GA-4 groups during the whole experimental course. The proliferation of mesangial cells was relieved and tubular desquamation was significantly inhibited in low-dose, mid-dose, high-dose Xieri GA-4 groups. Conclusion Xieri GA-4 has a protective effect on rat model of kidney injury induced by gentamicin, and has therapeutic effect on PI increase induced by kidney injury.
引文
[1] 魏云,吴爱萍,马丽芳,等.协日嘎四味汤胶囊主要药效学实验研究[J].中成药,2007,29(12):1738-1741.Wei Y,Wu AP,Ma LF,et al.Pharmacodynamics of Xieriga Siwei Tang Capsule[J].Chinese Traditional Patent Medicine,2007,29(12):1738-1741.
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[4] 李斌鑫,白凤,赵海龙,等.高效液相色谱法同时测定蒙药复方协日嘎-4中4种成分的含量[J].中南药学,2018,16(4):533-536.Li BX,Bai F,Zhao HL,et al.Simultaneous determination of the content of 4 effective components in compound Xieriga-4[J].Central South Pharmacy,2018,16(4):533-536.
[5] 白凤,李斌鑫,董玉,等.蒙药复方协日嘎-4的网络药理学研究[J].北京中医药大学学报,2018,41(2):140-147.Bai F,Li BX,Dong Y,et al.Network pharmacological studies of Mongolian compound Xieriga-4[J].Journal of Beijing University of Traditional Chinese Medicine,2018,41(2):140-147.
[6] 白凤,董玉,李斌鑫,等.蒙药复方协日嘎-4体内外化学成分分析[J].北京中医药大学学报,2018,41(10):835-841.Bai F,Li BX,Dong Y,et al.Analyzing chemical xomposition of Mongolian compound Xieriga-4 in vivo and in vitro[J].Journal of Beijing University of Traditional Chinese Medicine,2018,41(10):835-841.
[7] 王秀兰,韩斯日古楞,包春霞.三种蒙药一日多方与一日单方用法肾功能保护作用比较研究[J].辽宁中医杂志,2012,39(6):972-974.Wang XL,Han SRGL,Bao CX.Comparisons of renal protective effects between multi-day and single-day administrations of three Mongolian medicine[J].Liaoning Journal of Traditional Chinese Medicine,2012,39(6):972-974.
[8] 王秀兰,金亮,哈旦宝力高.9种蒙药3种组合用法对肾损伤动物模型肾功能保护作用比较研究[J].辽宁中医杂志,2011,38(11):2276-2278.Wang XL,Jin L,Ha DBLG.Study on experimental renal protective effect of three dose combinations of nine common Mongolian compounds[J].Liaoning Journal of Traditional Chinese Medicine,2011,38(11):2276-2278.
[9] 朱永康,许履和.固精导浊法治疗慢性前列腺炎133例报告[J].中医杂志,1988(9):41-43.Zhu YK,Xu LH.Report of securing essence and removing turbid therapy for chronic prostatitis in 133 cases[J].Journal of Traditional Chinese Medicine,1988(9):41-43.
[10] 陈志强,谭志健.中医辨证治疗慢性前列腺炎317例疗效分析[J].广州中医药大学学报,1994,11(4):200-203.Chen ZQ,Tan ZJ.Treatment of chronic prostatitis by traditional Chinese medicine:an analysis of 317 cases[J].Journal of Guangzhou University of Traditional Chinese Medicine,1994,11(4):200-203.
[11] 林树栋.基于奇恒之腑理论研究补肾导浊颗粒治疗慢性非细菌性前列腺炎的临床研究[D].南京:南京中医药大学,2014.Lin SD.Theoretical and clinical research in treating chronic non-bacterial prostatits based on theoretical studies of the extraordinary fu-organ and Bushen Daozhuo Granule[D].Nanjing:Journal of Nanjing University of Traditional Chinese Medicine,2014.
[12] 徐应臣,张旭,张翠薇,等.L-肉毒碱对庆大霉素引起的急性肾衰竭的保护作用研究[J].中国医药导报,2012,9(7):28-29.Xu YC,Zhang X,Zhang CW,et al.Study on the protective effect of L-carnitine against gentamicin-induced renal failure[J].China Medical Herald,2012,9(7):28-29.
[13] 冉雯雯.Melatonin对大鼠庆大霉素急性中毒性肾损伤保护作用的相关研究[D].青岛:青岛大学,2007.Ran WW.The protective effect of taurine on the toxic acute renal injury in rats and its possible mechanisms[D].Qingdao:Qingdao University,2007.
[14] 张凯悦.当代急性肾损伤诊断标准的沿革[J].医学研究生学报,2013,26(1):98-102.Zhang KY.Evolution of contemporary diagnostic criteria for acute kidney injury[J].Journal of Medical Postgraduates,2013,26(1):98-102.
[15] Hsu CY,Mc Culloch CE,Fan D,et al.Community-based incidence of acute renal failure[J].Kidney Int,2007,72(2):208-212.
[16] Liangos O,Wald R,O’Bell JW,et al.Epidemiology and outcomes of acute renal failure in hospitalized patients:a national survey[J].Clin J Am Soc Nephrol,2006,1(1):43-51.
[17] 游梦祺.“和解少阳,通利三焦”法治疗慢性肾脏病基础上急性肾损伤的临床疗效研究[D].北京:北京中医药大学,2014.You MQ.Clinical efficacy of therapy of hejishaoyang and tonglisanjiao on acute kidney injury on the base of chronic kidney disease[D].Beijing:Beijing University of Chinese Medicine,2014.
[18] 季然.脓毒症急性肾损伤的中医证候分析及相关因素的回顾性研究[D].北京:北京中医药大学,2018.Ji R.Retrospectively study on TCM patterns and related factors in pus-toxin pattern of acute kidney injury[D].Beijing:Beijing University of Chinese Medicine,2018.
[19] 贾春晖,毛玲,罗晓红,等.尿mAlb/Cr、NAG联合检测在糖尿病肾病早期诊断中的价值[J].国际检验医学杂志,2017,38(13):1826-1828.Jia CH,Mao L,Luo XL,et al.Value of combined detection of urinary mAlb/Cr and NAG in early diagnosis of diabetic nephroathy[J].Int J Lab Med,2017,38(13):1826-1828.
[20] 吴莉春,林联韵,江峰.尿微量蛋白及尿酶联合检测在糖尿病早期肾损伤诊断中的临床意义[J].医学理论与实践,2016,29(15):2091-2093.Wu LC,Lin LY,Jiang F.Clinical significance of combined detection of urinary micro-protein and NAG in diagnosis of early diabetic renal injury[J].J Med Theor & Prac,2016,29(15):2091-2093.
[21] 石艳,王陆飞,罗萍,等.庆大霉素诱导急性肾损伤大鼠模型肾损伤分子-1的表达[J].中国生物制品学杂志,2010,23(7):700-703.Shi Y,Wang LF,Luo P,et al.Expression of kidney injury molecule-1 in rat model of acute kidndy injury induced by gentamycin[J].Chin J Biologicals,2010,23(7):700-703.
[22] 刘艳红,张晓燕,赵利军.肾康注射液对庆大霉素肾损伤的保护作用[J].中国药师,2015,18(4):548-552.Liu YH,Zhang XY,Zhao LJ.Protective effect of Shenkang Injections in rats with kidney injury induced by gentamicin[J].China Pharmacist,2015,18(4):548-552.
[23] 曾凡智,肖创清,黄志红,等.硫酸庆大霉素诱导大鼠急性肾损伤模型血和尿NGAL、KIM-1的变化及意义[J].实用预防医学,2016,23(2):140-143.Zeng FZ,Xiao CQ,Huang ZH,et al.Changes and significance of NGAL and KIM-1 in blood and urine in rat models of acute kidney injury induced by gentamicin sulfate[J].Pract Prev Med,2016,23(2):140-143.
[24] 汪宁,张冬霞,张素才,等.预测庆大霉素、多柔比星和腺嘌呤致大鼠肾损伤的生物标志物[J].中国药理学与毒理学杂志,2015,29(1):84-91.Wang N,Zhang DX,Zhang SC,et al.Biomarkers for kidney injury induced by gentamicin doxorubicin and adenine in rats[J].Chin J Pharmacol Toxicol,2015,29(1):84-91.
[2] 内蒙古卫生厅.内蒙古蒙成药标准[M].赤峰:内蒙古科技人民出版社,1984:265.Inner Mongolian Department of Health.Mongolian Patent Medicine Standards of Inner Mongolia[M].Chifeng:Inner Mongolia People’s Science and Technology Publishing House,1984:265.
[3] 高建华,李斌鑫,白凤,等.蒙药复方协日嘎四味化学成分的研究[J].北京中医药大学学报,2016,39(9):755-758.Gao JH,Li BX,Bai F,et al.Chemical component analysis of Mongolian medicine compound Xieriga-4[J].Journal of Beijing University of Traditional Chinese Medicine,2016,39(9):755- 758.
[4] 李斌鑫,白凤,赵海龙,等.高效液相色谱法同时测定蒙药复方协日嘎-4中4种成分的含量[J].中南药学,2018,16(4):533-536.Li BX,Bai F,Zhao HL,et al.Simultaneous determination of the content of 4 effective components in compound Xieriga-4[J].Central South Pharmacy,2018,16(4):533-536.
[5] 白凤,李斌鑫,董玉,等.蒙药复方协日嘎-4的网络药理学研究[J].北京中医药大学学报,2018,41(2):140-147.Bai F,Li BX,Dong Y,et al.Network pharmacological studies of Mongolian compound Xieriga-4[J].Journal of Beijing University of Traditional Chinese Medicine,2018,41(2):140-147.
[6] 白凤,董玉,李斌鑫,等.蒙药复方协日嘎-4体内外化学成分分析[J].北京中医药大学学报,2018,41(10):835-841.Bai F,Li BX,Dong Y,et al.Analyzing chemical xomposition of Mongolian compound Xieriga-4 in vivo and in vitro[J].Journal of Beijing University of Traditional Chinese Medicine,2018,41(10):835-841.
[7] 王秀兰,韩斯日古楞,包春霞.三种蒙药一日多方与一日单方用法肾功能保护作用比较研究[J].辽宁中医杂志,2012,39(6):972-974.Wang XL,Han SRGL,Bao CX.Comparisons of renal protective effects between multi-day and single-day administrations of three Mongolian medicine[J].Liaoning Journal of Traditional Chinese Medicine,2012,39(6):972-974.
[8] 王秀兰,金亮,哈旦宝力高.9种蒙药3种组合用法对肾损伤动物模型肾功能保护作用比较研究[J].辽宁中医杂志,2011,38(11):2276-2278.Wang XL,Jin L,Ha DBLG.Study on experimental renal protective effect of three dose combinations of nine common Mongolian compounds[J].Liaoning Journal of Traditional Chinese Medicine,2011,38(11):2276-2278.
[9] 朱永康,许履和.固精导浊法治疗慢性前列腺炎133例报告[J].中医杂志,1988(9):41-43.Zhu YK,Xu LH.Report of securing essence and removing turbid therapy for chronic prostatitis in 133 cases[J].Journal of Traditional Chinese Medicine,1988(9):41-43.
[10] 陈志强,谭志健.中医辨证治疗慢性前列腺炎317例疗效分析[J].广州中医药大学学报,1994,11(4):200-203.Chen ZQ,Tan ZJ.Treatment of chronic prostatitis by traditional Chinese medicine:an analysis of 317 cases[J].Journal of Guangzhou University of Traditional Chinese Medicine,1994,11(4):200-203.
[11] 林树栋.基于奇恒之腑理论研究补肾导浊颗粒治疗慢性非细菌性前列腺炎的临床研究[D].南京:南京中医药大学,2014.Lin SD.Theoretical and clinical research in treating chronic non-bacterial prostatits based on theoretical studies of the extraordinary fu-organ and Bushen Daozhuo Granule[D].Nanjing:Journal of Nanjing University of Traditional Chinese Medicine,2014.
[12] 徐应臣,张旭,张翠薇,等.L-肉毒碱对庆大霉素引起的急性肾衰竭的保护作用研究[J].中国医药导报,2012,9(7):28-29.Xu YC,Zhang X,Zhang CW,et al.Study on the protective effect of L-carnitine against gentamicin-induced renal failure[J].China Medical Herald,2012,9(7):28-29.
[13] 冉雯雯.Melatonin对大鼠庆大霉素急性中毒性肾损伤保护作用的相关研究[D].青岛:青岛大学,2007.Ran WW.The protective effect of taurine on the toxic acute renal injury in rats and its possible mechanisms[D].Qingdao:Qingdao University,2007.
[14] 张凯悦.当代急性肾损伤诊断标准的沿革[J].医学研究生学报,2013,26(1):98-102.Zhang KY.Evolution of contemporary diagnostic criteria for acute kidney injury[J].Journal of Medical Postgraduates,2013,26(1):98-102.
[15] Hsu CY,Mc Culloch CE,Fan D,et al.Community-based incidence of acute renal failure[J].Kidney Int,2007,72(2):208-212.
[16] Liangos O,Wald R,O’Bell JW,et al.Epidemiology and outcomes of acute renal failure in hospitalized patients:a national survey[J].Clin J Am Soc Nephrol,2006,1(1):43-51.
[17] 游梦祺.“和解少阳,通利三焦”法治疗慢性肾脏病基础上急性肾损伤的临床疗效研究[D].北京:北京中医药大学,2014.You MQ.Clinical efficacy of therapy of hejishaoyang and tonglisanjiao on acute kidney injury on the base of chronic kidney disease[D].Beijing:Beijing University of Chinese Medicine,2014.
[18] 季然.脓毒症急性肾损伤的中医证候分析及相关因素的回顾性研究[D].北京:北京中医药大学,2018.Ji R.Retrospectively study on TCM patterns and related factors in pus-toxin pattern of acute kidney injury[D].Beijing:Beijing University of Chinese Medicine,2018.
[19] 贾春晖,毛玲,罗晓红,等.尿mAlb/Cr、NAG联合检测在糖尿病肾病早期诊断中的价值[J].国际检验医学杂志,2017,38(13):1826-1828.Jia CH,Mao L,Luo XL,et al.Value of combined detection of urinary mAlb/Cr and NAG in early diagnosis of diabetic nephroathy[J].Int J Lab Med,2017,38(13):1826-1828.
[20] 吴莉春,林联韵,江峰.尿微量蛋白及尿酶联合检测在糖尿病早期肾损伤诊断中的临床意义[J].医学理论与实践,2016,29(15):2091-2093.Wu LC,Lin LY,Jiang F.Clinical significance of combined detection of urinary micro-protein and NAG in diagnosis of early diabetic renal injury[J].J Med Theor & Prac,2016,29(15):2091-2093.
[21] 石艳,王陆飞,罗萍,等.庆大霉素诱导急性肾损伤大鼠模型肾损伤分子-1的表达[J].中国生物制品学杂志,2010,23(7):700-703.Shi Y,Wang LF,Luo P,et al.Expression of kidney injury molecule-1 in rat model of acute kidndy injury induced by gentamycin[J].Chin J Biologicals,2010,23(7):700-703.
[22] 刘艳红,张晓燕,赵利军.肾康注射液对庆大霉素肾损伤的保护作用[J].中国药师,2015,18(4):548-552.Liu YH,Zhang XY,Zhao LJ.Protective effect of Shenkang Injections in rats with kidney injury induced by gentamicin[J].China Pharmacist,2015,18(4):548-552.
[23] 曾凡智,肖创清,黄志红,等.硫酸庆大霉素诱导大鼠急性肾损伤模型血和尿NGAL、KIM-1的变化及意义[J].实用预防医学,2016,23(2):140-143.Zeng FZ,Xiao CQ,Huang ZH,et al.Changes and significance of NGAL and KIM-1 in blood and urine in rat models of acute kidney injury induced by gentamicin sulfate[J].Pract Prev Med,2016,23(2):140-143.
[24] 汪宁,张冬霞,张素才,等.预测庆大霉素、多柔比星和腺嘌呤致大鼠肾损伤的生物标志物[J].中国药理学与毒理学杂志,2015,29(1):84-91.Wang N,Zhang DX,Zhang SC,et al.Biomarkers for kidney injury induced by gentamicin doxorubicin and adenine in rats[J].Chin J Pharmacol Toxicol,2015,29(1):84-91.
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