目的 探讨胸腺素β4腹腔注射给药对重症性胰腺炎大鼠的保护作用及机制.方法 雄性SD大鼠54只,随机(随机数字法)分为3组:假手术组(SO组)、重症急性胰腺炎组(SAP组)、胸腺素β4预处理组(Tβ4组),每组18只.采用5％牛磺胆酸钠逆行胆胰管注射制备大鼠SAP模型,Tβ4组在造模前30 min经腹腔注射胸腺素β4(6 mg/kg),术后3、6、12h分批剖杀大鼠,各时间点6只.检测血清淀粉酶、TNF-α、IL-1β及IL-6水平,光镜观察胰头部组织病理变化,Western blot检测胰腺组织NF-κB p65和IκB α蛋白表达水平.多个样本均数比较采用单因素方差分析,两组间比较采用t检验.结果 SAP组(3、6、12 h)血清淀粉酶分别为(3221 ±394) U/L、(4509±474) U/L和(6280±728) U/L,高于相应时间点Tβ4组的(2598±416) U/L、(3639±373) U/L和(4782±466) U/L,差异具有统计学意义(t=-2.666,-3.530,-4.245,P＜0.05);SAP组(3、6、12 h)TNF-α分别为(247.7±18.5) pg/mL、(313.5±17.7) pg/mL和(359.3±22.6)pg/mL,均高于Tβ4组相应时间点的(182.3 ±13.6) pg/mL、(258.9±14.9)pg/mL和(278.1±16.3)pg/mL,差异具有统计学意义(t=-6.964,-5.769,-7.152,P＜0.05);SAP组(3、6、12 h)IL-1β分别为(258.2±10.5) pg/mL、(345.1±22.0) pg/mL和(430.9±25.4) pg/mL,均高于Tβ4组相应时间点的(170.3±12.4) pg/mL、(263.5±13.3) pg/mL和(303.7±16.1)pg/mL,差异具有统计学意义(t=-13.258,-7.762,-10.355,P＜0.05);SAP组(3、6、12 h)IL-6分别为(266.3±11.5) pg/mL、(355.0±24.4) pg/mL和(429.2±33.7) pg/mL,均高于Tβ4组相应时间点的(171.1±13.0) pg/mL、(234.9±19.2) pg/mL和(277.2±19.2)pg/mL,差异具有统计学意义(t=-13.401,-9.474,-9.582,P＜0.05);SAP组(3、6、12 h)胰腺病理评分分别为(6.25±0.94)分、(8.83 ±0.82)分和(12.08±1.16)分,显著高于Tβ4组相应时间点的(4.17±0.93)分、(6.33 ±0.82)分和(7.33±1.25)分,差异具有统计学意义(t=-3.867,-5.303,-6.823,P＜0.05).SO (12 h)组胰腺组织NF-κBp65蛋白相对表达量为0.95 ±0.11,显著低于SAP(12 h)组的(2.40±0.17),差异具有统计学意义(t=-17.368,P＜0.05),Tβ4组胰腺组织NF-κB p65蛋白相对表达量为(1.50 ±0.10),较SAP (12 h)组显著降低,差异具有统计学意义(t=10.917,P＜0.05).SO (12h)组胰腺组织IκB α蛋白相对表达量为(1.93±0.11),显著高于SAP (12 h)组的(0.78±0.18),差异具有统计学意义(t=13.260,P＜0.05),而Tβ4 (12 h)组胰腺组织IκB α蛋白相对表达量为(1.12±0.10),较SAP (12 h)组显著升高,差异具有统计学意义(t=4.112,P＜0.05).结论 胸腺素β4对重症急性胰腺炎大鼠具有保护作用.其作用机制可能与抑制胰腺NF-κB信号通路的活化及降低炎症细胞因子的水平有关.
目的 探討胸腺素β4腹腔註射給藥對重癥性胰腺炎大鼠的保護作用及機製.方法 雄性SD大鼠54隻,隨機(隨機數字法)分為3組:假手術組(SO組)、重癥急性胰腺炎組(SAP組)、胸腺素β4預處理組(Tβ4組),每組18隻.採用5％牛磺膽痠鈉逆行膽胰管註射製備大鼠SAP模型,Tβ4組在造模前30 min經腹腔註射胸腺素β4(6 mg/kg),術後3、6、12h分批剖殺大鼠,各時間點6隻.檢測血清澱粉酶、TNF-α、IL-1β及IL-6水平,光鏡觀察胰頭部組織病理變化,Western blot檢測胰腺組織NF-κB p65和IκB α蛋白錶達水平.多箇樣本均數比較採用單因素方差分析,兩組間比較採用t檢驗.結果 SAP組(3、6、12 h)血清澱粉酶分彆為(3221 ±394) U/L、(4509±474) U/L和(6280±728) U/L,高于相應時間點Tβ4組的(2598±416) U/L、(3639±373) U/L和(4782±466) U/L,差異具有統計學意義(t=-2.666,-3.530,-4.245,P＜0.05);SAP組(3、6、12 h)TNF-α分彆為(247.7±18.5) pg/mL、(313.5±17.7) pg/mL和(359.3±22.6)pg/mL,均高于Tβ4組相應時間點的(182.3 ±13.6) pg/mL、(258.9±14.9)pg/mL和(278.1±16.3)pg/mL,差異具有統計學意義(t=-6.964,-5.769,-7.152,P＜0.05);SAP組(3、6、12 h)IL-1β分彆為(258.2±10.5) pg/mL、(345.1±22.0) pg/mL和(430.9±25.4) pg/mL,均高于Tβ4組相應時間點的(170.3±12.4) pg/mL、(263.5±13.3) pg/mL和(303.7±16.1)pg/mL,差異具有統計學意義(t=-13.258,-7.762,-10.355,P＜0.05);SAP組(3、6、12 h)IL-6分彆為(266.3±11.5) pg/mL、(355.0±24.4) pg/mL和(429.2±33.7) pg/mL,均高于Tβ4組相應時間點的(171.1±13.0) pg/mL、(234.9±19.2) pg/mL和(277.2±19.2)pg/mL,差異具有統計學意義(t=-13.401,-9.474,-9.582,P＜0.05);SAP組(3、6、12 h)胰腺病理評分分彆為(6.25±0.94)分、(8.83 ±0.82)分和(12.08±1.16)分,顯著高于Tβ4組相應時間點的(4.17±0.93)分、(6.33 ±0.82)分和(7.33±1.25)分,差異具有統計學意義(t=-3.867,-5.303,-6.823,P＜0.05).SO (12 h)組胰腺組織NF-κBp65蛋白相對錶達量為0.95 ±0.11,顯著低于SAP(12 h)組的(2.40±0.17),差異具有統計學意義(t=-17.368,P＜0.05),Tβ4組胰腺組織NF-κB p65蛋白相對錶達量為(1.50 ±0.10),較SAP (12 h)組顯著降低,差異具有統計學意義(t=10.917,P＜0.05).SO (12h)組胰腺組織IκB α蛋白相對錶達量為(1.93±0.11),顯著高于SAP (12 h)組的(0.78±0.18),差異具有統計學意義(t=13.260,P＜0.05),而Tβ4 (12 h)組胰腺組織IκB α蛋白相對錶達量為(1.12±0.10),較SAP (12 h)組顯著升高,差異具有統計學意義(t=4.112,P＜0.05).結論 胸腺素β4對重癥急性胰腺炎大鼠具有保護作用.其作用機製可能與抑製胰腺NF-κB信號通路的活化及降低炎癥細胞因子的水平有關.
목적 탐토흉선소β4복강주사급약대중증성이선염대서적보호작용급궤제.방법 웅성SD대서54지,수궤(수궤수자법)분위3조:가수술조(SO조)、중증급성이선염조(SAP조)、흉선소β4예처리조(Tβ4조),매조18지.채용5％우광담산납역행담이관주사제비대서SAP모형,Tβ4조재조모전30 min경복강주사흉선소β4(6 mg/kg),술후3、6、12h분비부살대서,각시간점6지.검측혈청정분매、TNF-α、IL-1β급IL-6수평,광경관찰이두부조직병리변화,Western blot검측이선조직NF-κB p65화IκB α단백표체수평.다개양본균수비교채용단인소방차분석,량조간비교채용t검험.결과 SAP조(3、6、12 h)혈청정분매분별위(3221 ±394) U/L、(4509±474) U/L화(6280±728) U/L,고우상응시간점Tβ4조적(2598±416) U/L、(3639±373) U/L화(4782±466) U/L,차이구유통계학의의(t=-2.666,-3.530,-4.245,P＜0.05);SAP조(3、6、12 h)TNF-α분별위(247.7±18.5) pg/mL、(313.5±17.7) pg/mL화(359.3±22.6)pg/mL,균고우Tβ4조상응시간점적(182.3 ±13.6) pg/mL、(258.9±14.9)pg/mL화(278.1±16.3)pg/mL,차이구유통계학의의(t=-6.964,-5.769,-7.152,P＜0.05);SAP조(3、6、12 h)IL-1β분별위(258.2±10.5) pg/mL、(345.1±22.0) pg/mL화(430.9±25.4) pg/mL,균고우Tβ4조상응시간점적(170.3±12.4) pg/mL、(263.5±13.3) pg/mL화(303.7±16.1)pg/mL,차이구유통계학의의(t=-13.258,-7.762,-10.355,P＜0.05);SAP조(3、6、12 h)IL-6분별위(266.3±11.5) pg/mL、(355.0±24.4) pg/mL화(429.2±33.7) pg/mL,균고우Tβ4조상응시간점적(171.1±13.0) pg/mL、(234.9±19.2) pg/mL화(277.2±19.2)pg/mL,차이구유통계학의의(t=-13.401,-9.474,-9.582,P＜0.05);SAP조(3、6、12 h)이선병리평분분별위(6.25±0.94)분、(8.83 ±0.82)분화(12.08±1.16)분,현저고우Tβ4조상응시간점적(4.17±0.93)분、(6.33 ±0.82)분화(7.33±1.25)분,차이구유통계학의의(t=-3.867,-5.303,-6.823,P＜0.05).SO (12 h)조이선조직NF-κBp65단백상대표체량위0.95 ±0.11,현저저우SAP(12 h)조적(2.40±0.17),차이구유통계학의의(t=-17.368,P＜0.05),Tβ4조이선조직NF-κB p65단백상대표체량위(1.50 ±0.10),교SAP (12 h)조현저강저,차이구유통계학의의(t=10.917,P＜0.05).SO (12h)조이선조직IκB α단백상대표체량위(1.93±0.11),현저고우SAP (12 h)조적(0.78±0.18),차이구유통계학의의(t=13.260,P＜0.05),이Tβ4 (12 h)조이선조직IκB α단백상대표체량위(1.12±0.10),교SAP (12 h)조현저승고,차이구유통계학의의(t=4.112,P＜0.05).결론 흉선소β4대중증급성이선염대서구유보호작용.기작용궤제가능여억제이선NF-κB신호통로적활화급강저염증세포인자적수평유관.
Objective To investigate the protective effects and mechanisms of intraperitoneal administration of thymosin β4 on severe acute pancreatitis in rats.Methods Fifty-four male Sprague-Dawley rats were randomly (random number) divided into sham operation (SO) group,severe acute pancreatitis (SAP) group and thymosin β4 (Tβ4) pretreatment group (n =18 in each group).SAP rat model was prepared by retrograde injection of 5％ sodium taurocholate into the biliopancreatic duct.Rats in Tβ4 group were treated with thymosin β4 (6 mg/kg) by intraperitoneal administration prior to SAP modeling.Six rats in each group were sacrificed at 3,6,12 hours,respectively after modeling.The serum levels of amylase,tumor necrosis factor-α (TNF-α),interleukin-1 β (IL-1 β),and interleukin-6 (IL-6)were detected,and pathological scores of the tissue of pancreas head were evaluated under light microscope.Pancreatic nuclear factor-kappa 1B (NF-κB) p65 and IκB α levels were detected by the Western blot.All data were analyzed by using the analysis of variauce or t test.Results The levels of serum amylase of SAP 3,6 and 12 hours groups were (3221 ±394) U/L,(4509 ±474) U/L and (6280 ±728) U/L,which were significantly higher than (2598±416) U/L,(3639 ±373) U/L and (4782 ±466) U/L of the Tβ4 groups (t =-2.666,-3.530,-4.245,P ＜ 0.05).The levels of serum TNF-α of the SAP 3,6 and 12 hours groups were (247.7 ± 18.5) pg/mL,(313.5 ± 17.7) pg/mL and (359.3 ±22.6) pg/mL,which were higher than (182.3 ± 13.6) pg/mL,(258.9 ± 14.9) pg/mL and (278.1 ± 16.3) pg/mL of the Tβ4 groups (t =-6.964,-5.769,-7.152,P ＜ 0.05).The levels of serum IL-1 β of the SAP 3,6 and 12 hours groups were (258.2±10.5) pg/mL,(345.1 ±22.0) pg/mL and (430.9 ±25.4) pg/mL,which were higher than (170.3 ± 12.4) pg/mL,(263.5 ± 13.3) pg/mL and (303.7 ± 16.1) pg/mL of the Tβ4 groups (t =-13.258,-7.762,-10.355,P ＜ 0.05).The levels of serum IL-6 of SAP 3,6 and 12 hours groups were (266.3 ±11.5) pg/mL,(355.0 ±24.4) pg/mL and (429.2 ±33.7) pg/ mL,which were higher than (171.1 ± 13.0) pg/mL,(234.9 ± 19.2) pg/mL and (277.2 ± 19.2) pg/ mL of the Tβ4 groups (t =-13.401,-9.474,-9.582,P ＜ 0.05).The pancreatic pathological scores of the SAP3,6 and 12 hours groups were (6.25 ±0.94),(8.83 ±0.82) and (12.08 ±1.16),which were higher than (4.17 ± 0.93),(6.33 ± 0.82) and (7.33 ± 1.25) of the Tβ4 groups (t =-3.867,-5.303,-6.823,P ＜ 0.05).The relative expression of pancreatic NF-κB p65 in SO group was (0.95 ±0.11),which was significantly lower than (2.40 ±0.17) of the SAP 12 hours group (t =-17.368,P＜ 0.05).The relative expression of pancreatic NF-κB p65 in Tβ4 group was 1.50 ± 0.10,which was significantly lower than SAP 12 hours group (t =10.917,P ＜0.05).The relative expression of pancreatic IκB α in SO group was (1.93 ±0.11),which was significantly higher than (0.78 ±0.18) of the SAP 12 hours group (t =13.260,P ＜ 0.05).The relative expression of pancreatic IκB α in Tβ4 group was (1.12±0.10),which was significantly higher than SAP 12 hours group (t =-4.112,P ＜ 0.05).Conclusions Thymosin β4 has the protective effect on SAP rat model,and the mechanism may be associated with inhibition of NF-κB signaling pathway and decreased proinflammatory cytokines.
