中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
CHINESE JOURNAL OF EXPERIMENTAL SURGERY
2013年
3期
527-529
,共3页
李红光%刘红山%薛焕洲%岳学良%余淼%潘承恩
李紅光%劉紅山%薛煥洲%嶽學良%餘淼%潘承恩
리홍광%류홍산%설환주%악학량%여묘%반승은
急性胰腺炎%p38丝裂原活化蛋白激酶%肾损伤%肿瘤坏死因子
急性胰腺炎%p38絲裂原活化蛋白激酶%腎損傷%腫瘤壞死因子
급성이선염%p38사렬원활화단백격매%신손상%종류배사인자
Acute pancreatitis%p38 mitogen-activated protein kinases%Renal injury%Tumour necrosis factor
目的 观察大鼠急性出血坏死性胰腺炎(ANP)肾损伤的机制及其p38丝裂原活化蛋白激酶(MAPK)抑制剂的治疗作用.方法 60只SD大鼠,随机分为3组,Sham组、ANP组和SB治疗组(SB203580,0.5 mg/kg静脉注射).采用5%牛磺胆酸钠溶液逆行注射胰胆管建立鼠的ANP模型,大鼠分别在术后1、3、6、12 h剖杀.检测血肿瘤坏死因子-α(TNF-α)、淀粉酶、血尿素氮(BUN)、血尿素氮(Cr)、β2-微球蛋白(β2-MG)水平;光镜和电镜下检测胰腺及其肾组织的病理变化;免疫组织化学检测肾脏组织中p38MAPK的表达.结果 ANP组血BUN[(15.68±1.85) mmol/L],Cr[(30.60±2.04) mmol/L]、β2-MG[(31.40±1.93) mmol/L],血和肾脏组织中的TNF-α[血(257.40±4.52) ng/L,肾脏(203.01±5.38) ng/L]较Sham组[BUN (0.31±1.08) mmol/L,Cr(21.62±1.75) mmol/L,β2-MG (21.12±1.65) mmol/L、(36.90 ±0.52) ng/L、(31.08±1.12) ng/L]显著升高(P<0.05);肾脏组织中的p38MAPK的表达也显著增强;SB203580治疗组较ANP组可显著减低血BUN[(11.93±1.77) mmol/L]、Cr[(24.73 ±l.01) mmol/L]、β2-MG[(25.81±2.21) mmol/L]、血和肾组织中的TNF-α[(199.73±8.23) ng/L,(173.06±4.89) ng/L]及其肾组织中的p38MAPK的表达;光镜下及其电镜下检测肾脏的损害显著减轻.结论 p38MAPK可能参与了ANP并发的肾损伤,p38MAPK抑制剂(SB203580)对ANP肾损伤有治疗作用.
目的 觀察大鼠急性齣血壞死性胰腺炎(ANP)腎損傷的機製及其p38絲裂原活化蛋白激酶(MAPK)抑製劑的治療作用.方法 60隻SD大鼠,隨機分為3組,Sham組、ANP組和SB治療組(SB203580,0.5 mg/kg靜脈註射).採用5%牛磺膽痠鈉溶液逆行註射胰膽管建立鼠的ANP模型,大鼠分彆在術後1、3、6、12 h剖殺.檢測血腫瘤壞死因子-α(TNF-α)、澱粉酶、血尿素氮(BUN)、血尿素氮(Cr)、β2-微毬蛋白(β2-MG)水平;光鏡和電鏡下檢測胰腺及其腎組織的病理變化;免疫組織化學檢測腎髒組織中p38MAPK的錶達.結果 ANP組血BUN[(15.68±1.85) mmol/L],Cr[(30.60±2.04) mmol/L]、β2-MG[(31.40±1.93) mmol/L],血和腎髒組織中的TNF-α[血(257.40±4.52) ng/L,腎髒(203.01±5.38) ng/L]較Sham組[BUN (0.31±1.08) mmol/L,Cr(21.62±1.75) mmol/L,β2-MG (21.12±1.65) mmol/L、(36.90 ±0.52) ng/L、(31.08±1.12) ng/L]顯著升高(P<0.05);腎髒組織中的p38MAPK的錶達也顯著增彊;SB203580治療組較ANP組可顯著減低血BUN[(11.93±1.77) mmol/L]、Cr[(24.73 ±l.01) mmol/L]、β2-MG[(25.81±2.21) mmol/L]、血和腎組織中的TNF-α[(199.73±8.23) ng/L,(173.06±4.89) ng/L]及其腎組織中的p38MAPK的錶達;光鏡下及其電鏡下檢測腎髒的損害顯著減輕.結論 p38MAPK可能參與瞭ANP併髮的腎損傷,p38MAPK抑製劑(SB203580)對ANP腎損傷有治療作用.
목적 관찰대서급성출혈배사성이선염(ANP)신손상적궤제급기p38사렬원활화단백격매(MAPK)억제제적치료작용.방법 60지SD대서,수궤분위3조,Sham조、ANP조화SB치료조(SB203580,0.5 mg/kg정맥주사).채용5%우광담산납용액역행주사이담관건립서적ANP모형,대서분별재술후1、3、6、12 h부살.검측혈종류배사인자-α(TNF-α)、정분매、혈뇨소담(BUN)、혈뇨소담(Cr)、β2-미구단백(β2-MG)수평;광경화전경하검측이선급기신조직적병리변화;면역조직화학검측신장조직중p38MAPK적표체.결과 ANP조혈BUN[(15.68±1.85) mmol/L],Cr[(30.60±2.04) mmol/L]、β2-MG[(31.40±1.93) mmol/L],혈화신장조직중적TNF-α[혈(257.40±4.52) ng/L,신장(203.01±5.38) ng/L]교Sham조[BUN (0.31±1.08) mmol/L,Cr(21.62±1.75) mmol/L,β2-MG (21.12±1.65) mmol/L、(36.90 ±0.52) ng/L、(31.08±1.12) ng/L]현저승고(P<0.05);신장조직중적p38MAPK적표체야현저증강;SB203580치료조교ANP조가현저감저혈BUN[(11.93±1.77) mmol/L]、Cr[(24.73 ±l.01) mmol/L]、β2-MG[(25.81±2.21) mmol/L]、혈화신조직중적TNF-α[(199.73±8.23) ng/L,(173.06±4.89) ng/L]급기신조직중적p38MAPK적표체;광경하급기전경하검측신장적손해현저감경.결론 p38MAPK가능삼여료ANP병발적신손상,p38MAPK억제제(SB203580)대ANP신손상유치료작용.
Objective To investigate the mechanism of kidney injury in experimental acute necrotic panceatitis (ANP) and protective effects of p38 mitogen-activated protein kinase (MAPK) inhibitor.Methods Sixty pathogen-free male Sprague-Dawley rats were randomly divided into the sham group,acute necrotizing pancreatitis group (ANP group) and ANP group of rats subject to treatment of SB203580 (SB203580,0.5 mg/kg,i.v).The rats were sacrificed at 1,3,6 and 12 h after operation.The serum levels of blood urea nitrogen (BUN),creatinine (Cr),β 2-Microglobulin (β2-MG),and serum and renal tissue levels of tumor necrosis factor-α (TNF-α) were determined.The expression levels of pho-p38 MAPK in the pancreas and kidney of SAP rats were determined by using immunohistochemistry.Pathologic changes of the kidney and pancreas were observed under light microscope and electron microscope.Results The serum levels of BUN [(15.68 ± 1.85) mmol/L],Cr [(30.60 ±2.04) mmol/L],β2-MG [(31.40 ±1.93) mmol/L],serum and renal tissue levels of TNF-α [serum:(257.40 ±4.52) ng/L,renal tissue:(203.01 ±5.38) ng/L],and the expression of p38 MAPK in the pancreas and kidney in ANP group and SB group were more significantly increased than those in sham group [BUN (0.31 ± 1.08) mmol/L; Cr (21.62 ±1.75) mmol/L; β2-MG (21.12 ± 1.65) mmol/L; TNF-α,pancreas:(36.90 ±0.52) ng/L,and kidney:(31.08 ± 1.12) ng/L] (P <0.05).Moreover,Those in SB group were more significantly reduced [BUN (11.93 ±1.77) mmol/L,Cr (24.73 ± 1.01) mmol/L,β2-MG (25.81 ±2.21) mmol/L,TNF-α:pancreas,(199.73 ± 8.23) ng/L,and kidney:(173.06 ± 4.89) ng/L] than those in SAP group (P < 0.05).The renal sections from SB group displayed significantly less proximal tubule cell necrosis than in ANP group.Conclusion The activation and over-expression of 38 MAPK in the renal tissue may be one of the reasons for renal injury in ANP,and SB203580 can be used to treat the ANP-associated renal injury through down-regulating the expression of p38 MAPK.