中华危重症医学杂志(电子版)
中華危重癥醫學雜誌(電子版)
중화위중증의학잡지(전자판)
CHINESE JOURNAL OF CRITICAL CARE MEDICINE ( ELECTRONIC EDITON)
2015年
3期
143-149
,共7页
石占利%李国辉%孙静%方堃%赵金峰%蔡丹莉%高凯%陈芝芸
石佔利%李國輝%孫靜%方堃%趙金峰%蔡丹莉%高凱%陳芝蕓
석점리%리국휘%손정%방곤%조금봉%채단리%고개%진지예
重症急性胰腺炎%急性肺损伤%大黄素%大鼠
重癥急性胰腺炎%急性肺損傷%大黃素%大鼠
중증급성이선염%급성폐손상%대황소%대서
Severe acute pancreatitis%Acute lung injury%Emodin%Rats
目的:探讨大黄素在重症急性胰腺炎并发急性肺损伤大鼠细胞凋亡中的干预作用。方法采用逆行胰胆管注射牛磺胆酸法进行造模。造模后将136只大鼠分为4组:大黄素低剂量组(大黄素10 mg/kg)、大黄素中剂量组(大黄素20 mg/kg)、大黄素高剂量组(大黄素40 mg/kg)和对照组。各剂量组大鼠分别在造模前后1 h分别按照1 ml/100 g体质量的标准经腹腔注射相应剂量的大黄素。于造模后3、6、12、24 h分别观察并评估肺组织病理变化。采用酶化学法检测肺组织髓过氧化物酶(MPO),DNA断裂的原位末端标记(TUNEL)法测定细胞凋亡并计算凋亡指数,实时荧光定量逆转录-多聚酶链反应(RT-PCR)法检测肺组织Notch-1,Hes-1,Hes-5的mRNA表达水平。结果对照组、低剂量组、中剂量组、高剂量组肺组织病理评分分别为(3.0±1.7)、(1.9±1.2)、(1.6±1.2)及(1.4±1.1)分,MPO水平分别为(5.4±1.1)、(4.8±0.9)、(4.5±0.9)及(4.1±0.7)U/g,细胞凋亡指数分别为(21.0±4.3)、(24.4±5.1)、(26.7±5.1)及(28.7±5.9)%。大黄素各剂量组在肺组织病理评分、MPO水平及细胞凋亡指数方面均明显优于对照组(P均<0.05)。对照组、低剂量组、中剂量组、高剂量组肺组织Notch-1 mRNA分别为(0.65±0.16)、(0.99±0.37)、(1.05±0.37)及(1.32±0.66),Hes-1 mRNA分别为(0.70±0.19)、(0.97±0.27)、(1.05±0.33)及(1.11±0.36),Hes-5 mRNA分别为(0.77±0.43)、(1.04±0.68)、(1.65±1.48)、(2.73±3.40)。大黄素各剂量组Notch-1 mRNA及Hes-1 mRNA的表达均较对照组显著增加(P均<0.05),而Hes-5 mRNA表达仅高剂量组与对照组、低剂量组及中剂量组比较,差异有统计学意义(P均<0.05)。结论重症急性胰腺炎并发急性肺损伤时,大黄素可以促进肺组织炎症细胞凋亡,从而减轻肺损伤程度;Notch/Hes信号通路可能是大黄素调控肺组织细胞凋亡的重要途径。
目的:探討大黃素在重癥急性胰腺炎併髮急性肺損傷大鼠細胞凋亡中的榦預作用。方法採用逆行胰膽管註射牛磺膽痠法進行造模。造模後將136隻大鼠分為4組:大黃素低劑量組(大黃素10 mg/kg)、大黃素中劑量組(大黃素20 mg/kg)、大黃素高劑量組(大黃素40 mg/kg)和對照組。各劑量組大鼠分彆在造模前後1 h分彆按照1 ml/100 g體質量的標準經腹腔註射相應劑量的大黃素。于造模後3、6、12、24 h分彆觀察併評估肺組織病理變化。採用酶化學法檢測肺組織髓過氧化物酶(MPO),DNA斷裂的原位末耑標記(TUNEL)法測定細胞凋亡併計算凋亡指數,實時熒光定量逆轉錄-多聚酶鏈反應(RT-PCR)法檢測肺組織Notch-1,Hes-1,Hes-5的mRNA錶達水平。結果對照組、低劑量組、中劑量組、高劑量組肺組織病理評分分彆為(3.0±1.7)、(1.9±1.2)、(1.6±1.2)及(1.4±1.1)分,MPO水平分彆為(5.4±1.1)、(4.8±0.9)、(4.5±0.9)及(4.1±0.7)U/g,細胞凋亡指數分彆為(21.0±4.3)、(24.4±5.1)、(26.7±5.1)及(28.7±5.9)%。大黃素各劑量組在肺組織病理評分、MPO水平及細胞凋亡指數方麵均明顯優于對照組(P均<0.05)。對照組、低劑量組、中劑量組、高劑量組肺組織Notch-1 mRNA分彆為(0.65±0.16)、(0.99±0.37)、(1.05±0.37)及(1.32±0.66),Hes-1 mRNA分彆為(0.70±0.19)、(0.97±0.27)、(1.05±0.33)及(1.11±0.36),Hes-5 mRNA分彆為(0.77±0.43)、(1.04±0.68)、(1.65±1.48)、(2.73±3.40)。大黃素各劑量組Notch-1 mRNA及Hes-1 mRNA的錶達均較對照組顯著增加(P均<0.05),而Hes-5 mRNA錶達僅高劑量組與對照組、低劑量組及中劑量組比較,差異有統計學意義(P均<0.05)。結論重癥急性胰腺炎併髮急性肺損傷時,大黃素可以促進肺組織炎癥細胞凋亡,從而減輕肺損傷程度;Notch/Hes信號通路可能是大黃素調控肺組織細胞凋亡的重要途徑。
목적:탐토대황소재중증급성이선염병발급성폐손상대서세포조망중적간예작용。방법채용역행이담관주사우광담산법진행조모。조모후장136지대서분위4조:대황소저제량조(대황소10 mg/kg)、대황소중제량조(대황소20 mg/kg)、대황소고제량조(대황소40 mg/kg)화대조조。각제량조대서분별재조모전후1 h분별안조1 ml/100 g체질량적표준경복강주사상응제량적대황소。우조모후3、6、12、24 h분별관찰병평고폐조직병리변화。채용매화학법검측폐조직수과양화물매(MPO),DNA단렬적원위말단표기(TUNEL)법측정세포조망병계산조망지수,실시형광정량역전록-다취매련반응(RT-PCR)법검측폐조직Notch-1,Hes-1,Hes-5적mRNA표체수평。결과대조조、저제량조、중제량조、고제량조폐조직병리평분분별위(3.0±1.7)、(1.9±1.2)、(1.6±1.2)급(1.4±1.1)분,MPO수평분별위(5.4±1.1)、(4.8±0.9)、(4.5±0.9)급(4.1±0.7)U/g,세포조망지수분별위(21.0±4.3)、(24.4±5.1)、(26.7±5.1)급(28.7±5.9)%。대황소각제량조재폐조직병리평분、MPO수평급세포조망지수방면균명현우우대조조(P균<0.05)。대조조、저제량조、중제량조、고제량조폐조직Notch-1 mRNA분별위(0.65±0.16)、(0.99±0.37)、(1.05±0.37)급(1.32±0.66),Hes-1 mRNA분별위(0.70±0.19)、(0.97±0.27)、(1.05±0.33)급(1.11±0.36),Hes-5 mRNA분별위(0.77±0.43)、(1.04±0.68)、(1.65±1.48)、(2.73±3.40)。대황소각제량조Notch-1 mRNA급Hes-1 mRNA적표체균교대조조현저증가(P균<0.05),이Hes-5 mRNA표체부고제량조여대조조、저제량조급중제량조비교,차이유통계학의의(P균<0.05)。결론중증급성이선염병발급성폐손상시,대황소가이촉진폐조직염증세포조망,종이감경폐손상정도;Notch/Hes신호통로가능시대황소조공폐조직세포조망적중요도경。
Objective To clarify the intervention effect of emodin for the cell apoptosis in rats with severe acute pancreatitis associated with acute lung injury. Methods Retrograde pancreatic taurocholic acid injection method was used to establish the models. Then 136 rats were randomly divided into 4 groups: low dose group (10 mg/kg emodin), middle dose group (20 mg/kg emodin), high dose group (40 mg/kg emodin) and control group, 34 rats in each group. Rats in each group were respectively injected with experimental drugs into abdominal cavity at 1 h before and after modeling (following 1 ml/100 g of body weight). The specimens of each group were taken at 3, 6, 12, 24 h after the modeling. The pathological changes of lung tissue were evaluated, the myeloperoxidase (MPO) of lung tissue was examined by enzyme chemical method, the apoptosis was measured by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and the apoptosis index was then calculated. Notch-l mRNA, Hes-l mRNA and Hes-5 mRNA in lung tissue were detected by real-time quantitative reverse transcription polymerase chain reaction(RT-PCR). Results The lung tissue pathological score were (3.0 ± 1.7), (1.9 ± 1.2), (1.6 ± 1.2) and (1.4 ± 1.1) points, MPO levels were (5.4 ± 1.1), (4.8 ± 0.9), (4.5 ± 0.9) and (4.1 ± 0.7) U/g, apoptosis index were (21.0 ± 4.3), (24.4 ± 5.1), (26.7 ± 5.1) and (28.7 ± 5.9)%in controls, low dose group, middle dose group and high dose group, respectively. Compared with the control group, lung tissue pathological score, MPO levels and apoptosis index improved significantly in each dose group treated with emodin (all P<0.05). The expression of Notch-1 mRNA were (0.65 ± 0.16), (0.99 ± 0.37), (1.05 ± 0.37) and (1.32 ± 0.66), Hes-1 mRNA were (0.70 ± 0.19), (0.97 ± 0.27), (1.05 ± 0.33) and (1.11 ± 0.36), Hes-5 mRNA were (0.77 ± 0.43), (1.04 ± 0.68), (1.65 ± 1.48) and (2.73 ± 3.40) in controls, low dose group, middle dose group and high dose group, respectively. And the expression of Notch-1 mRNA and Hes-1 mRNA increased significantly in each dose group as compared with the control group (all P < 0.05), but the expression of Hes-5 mR NA only increased markedly among the high dose group with control group, low dose group and middle dose group (all P < 0.05). Conclusions Emodin canpromote inflammatory cell apoptosis in lung tissue when severe acute pancreatitis with lung injury, so as to decrease the degree of lung injury. Notch/Hes signaling pathway may be the important mechanism of emodin to regulate cell apoptosis in lung.