丹参预处理对肝脏缺血再灌注后胃肠激素的影响

目的探讨丹参预处理对肝脏缺血再灌注后胃肠激素的影响。方法前瞻性研究2010年5月至2012年5月广州军区武汉总医院收治的32例肝病患者，对所有患者行肝部分切除术，术中行第一肝门阻断。按随机数字表法将32例患者分为2组：缺血再灌注组（IR组，15例）和丹参预处理组（SM组，17例），两组患者均在术中行肝部分切除，以P6ngle法行第一肝门阻断约15～20min，IR组术前3d给予30mL／d生理盐水静脉滴注，SM组术前3d给予丹参注射液30mL／d静脉滴注；12例开腹手术而未行肝门阻断者作为阴性对照组（s0组）；5例健康志愿者作为正常对照组（CO组）。分别测定各组胃动素、胆囊收缩素、血管活性肠肽、胰泌素水平变化情况。多组比较采用单因素方差分析，两两比较采用LSD—t检验。结果c0组胃动素水平为（347±14）μg/L，SO组术后24、48、72h胃动素水平分别为（324±13）μg/L、（345±12）μg/L和（345±13）μg/L，IR组分别为（307±10）μg/L、（316±9）μg/L和（338±13）μg/L，SM组分别为（313±7）μg/L、（337±12）μg/L和（345±12）μg/L。s0组术后24h胃动素水平显著低于c0组（t=5．25，P〈0．05）；IR组术后24、48、72h胃动素水平显著低于同时相点sO组（t=10．05，8．09，2．07，P〈0．05）；SM组胃动素表达水平在术后24、48h显著低于SO组（t=9．83，2．28，P〈0．05），但是至术后72h与S0组比较，差异无统计学意义（t=0．36，P〉0．05）；SM组胃动素表达水平在术后24、48、72h显著高于IR组（t=3．80，7．10，2．35，P〈0．05）。CO组胆囊收缩素水平为（2．53±0．06）μg/L，SO组24、48、72h胆囊收缩素水平分别为（3．28±0．09）μg/L、（2．52±0．09）μg/L和（2．54±0．16）μg/L，IR组分别为（4．34±0．21）μg/L、（3．63±0．31）μg/L和（3．25±0．09）μg/L，SM组分别为（3．71±0．28）μg/L、（3．28±0．11）μg/L和（2．53±0．09）μg/L。SO组术后24h胆囊收缩素水平显著高于c0组（t=4．33，P〈0．05）；IR组术后24、48、72h胆囊收缩素水平显著高于同时相点的s0组（t=9．32，5．37，2．16，P〈0．05）；SM组胆囊收缩素表达水平在术后24、48h显著高于s0组（t=7．21，3．42，P〈0．05），但是至术后72h与S0组比较，差异无统计学意义（t=0．29，P〉0．05）。SM组胆囊收缩素表达水平在术后24、48、72h显著低于IR组（t=5．62，4．63，3．57，P〈0．05）。CO组血管活性肠肽水平为（11．8±1．6）μg/L，SO组术后24、48、72h血管活性肠肽水平分别为（21．5±3．8）μg/L、（12．2±1．6）μg/L和（11．9±1．7）μg/L，IR组分别为（29．7±4．1）μg/L、（22．9±4．2）μg/L和（18．8±2．8）μg/L，SM组分别为（22．4±4．1）μg/L、（16．4±2．3）μg/L和（12．1±1。6）彬L。s0组术后24h血管活性肠肽水平显著高于C0组（t=3．59，P〈0．05）；IR组患者血管活性肠肽表达水平在术后24、48、72h显著高于同时相点S0组（t=6．35，3．22，2．36，P〈0．05）。SM组患者血管活性肠肽表达水平在术后24、48h显著高于s0组（t=5．04，2．33，P〈0．05），但是至术后72h与s0组比较，差异无统计学意义（t=0．18，P〉0．05）。SM组患者血管活性肠肽表达水平在术后24、48、72h显著低于IR组（t=4．27，3．87，2．45，P〈0．05）。CO组胰泌素水平为（75±5）μg/L，SO组术后24、48、72h胰泌素水平分别为（98±6）μg/L、（76±4）μg/L和（76±4）μg/L，IR组分别为（129±6）μg/L、（102±8）μg/L和（89±6）μg/L，sM组分别为（104±8）μg/L、（90±6）μg/L和（74±4）μg/L。S0组术后24h胰泌素水平显著高于CO组（t=3．27，P〈0．05）；IR组患者胰泌素表达水平在术后24、48、72h显著高于同时相点s0组（t=5．20，2．94，1．77，P〈0．05）。SM组患者胰泌素表达水平在术后24、48h显著高于s0组（t=4．16，2．54，P〈0．05），但是至术后72h与SO组比较，差异无统计学意义（t=0．23，P〉0．05）。SM组患者胰泌素表达水平在术后24、48、72h显著低于IR组（t=5．13，4．32，2．87，P〈0．05）。结论肝门阻断所致胃肠道淤血可导致同期胃动素表达下调，胆囊收缩素、血管活性肠肽、胰泌素表达上升；丹参可能通过改善微循环、减轻胃肠道水肿，改善胃肠运动功能，间接影响胃肠激素的分泌表达。

Changes of gastrointestinal hormones before and after hepatic ischemia reperfusion and the role of salvia miltiorrhiza pretreatment

Objective To study the changes of gastrointestinal hormones before and after hepatic ischemia reperfusion and the role of salvia miltiorrhiza pretreatment. Methods The clinical data of 32 patients with hepatic diseases who were admitted to the Wuhan General Hospital of Guangzhou Military Area of PLA from May 2010 to May 2012 were prospectively analyzed. Thirty-two patients with hepatic inflow occlusion were randomly divided into the ischemia reperfusion group （IR group, 15 patients） and salvia miltiorrhiza pretreatment group （SM group, 17 patients）. Patients in the IR group and SM group received partial hepatectomy with hepatic inflow occlusion by Pringle maneuver for 15-20 minutes. Patients in the IR group and SM group were injected with normal saline and salvia miltiorrhiza （30 mL/d） by intravenous drip for 3 days before operation, respectively. Twelve patients with hepatic diseases who received open surgery without block of hepatic inflow occlusion were enrolled in the negative control group （SO group） and 5 healthy volunteers were enrolled in the normal control group （CO group）. The changes of the motilin, cholecystokinin, vasoactive intestinal peptide and secretin of the 4 groups were recorded. All data were analyzed using the analysis of variance or LSD-t test. Results The level of motilin of the CO group was （347 ± 14） μg/L. The levels of motilin of the SO group, IR group, and SM group at postoperative 24, 48 and 72 hours were （324 ± 13 ） μg/L, （345 ± 12） μg/L, （345 ± 13） μg/L, （307 ± 10） μg/L, （316 ±9） μg/L, （338 ± 13） μg/L, （313 ±7）μg/L, （337 ± 12）μg/L and （345 ± 12）μg/L, respectively. The level of motilin of the SO group at postoperative 24 hours was significantly lower than that of the CO group （ t = 5.25, P 〈 0.05 ） ; the levels of motilin of the IR group at postoperative 24, 48 and 72 hours were significantly lower than those of the SO group （ t = 10. 05, 8.09, 2. 07, P 〈 0.05 ） ; the levels of motilin of the SM group at postoperative 24 and 48 hours were significantly lower than those of the SO group （ t = 9. 83, 2. 28, P 〈 0.05 ）, while there was no significant difference in the level of motilin between the SM group and the SO group at postoperative 72 hours （ t = 0. 36, P 〉 0.05 ） ; the levels of motilin of the SM group at postoperative 24, 48 and 72 hours were significantly higher than those of the IR group （t = 3.80, 7. 10, 2. 35, P 〈 0.05）. The levels of cholecystokinin of the CO group was （2.53 ±0.06）μg/L. The levels of cholecystokinin of the SO group, IR group and SM group at postoperative 24 hours were （ 3.28 ± 0.09 ） μg/L, （ 2.52 ± 0.09 ） μg/L, （2.54 -± 0.16 ） μg/L, （4.34 ± 0.21 ） μg/L, （ 3.63 ± 0.31）μg/L, （3.25 ±0.09） μg/L, （3.71 ±0.28） μg/L, （3.28 ±0. 11） μg/L and （2.53 ±0.09）μg/L, respectively. The level of cholecystokinin of the SO group at postoperative 24 hours was significantly higher than that of the CO group （t =4. 33, P 〈0.05） ; the levels of cholecystokinin of the IR group at postoperative 24, 48 and 72 hours were significantly higher than those of the SO group （t =9. 32, 5.37, 2. 16, P 〈0.05） ; the levels of cholecystokinin of the SM group at postoperative 24 and 48 hours were significantly higher than those of the SO group （ t = 7. 21, 3. 42, P 〈 0.05 ）, while there was no significant difference in the level of cholecystokinin between the SM group and the SO group at postoperative 72 hours （ t = 0. 29, P 〉 0. 05 ） ; the levels of cholecystokinin of the SM group at postoperative 24, 48 and 72 hours were significantly higher than those of the IR group （ t = 5.62, 4. 63, 3.57, P 〈 0.05 ）. The level of vasoactive intestinal peptide of the CO group was （ 11.8 ± 1.6） μg/L. The levels of vasoactive intestinal peptide of the SO group, IR group, and SM group at postoperative 24, 48 and 72 hours were （21.5 ± 3.8 ） μg/L, （ 12.2 ± l. 6） μg/L, （ 11.9± 1.7 ） μg/L, （29.7 ± 4.1 ） μg/L, （22.9±4.2）μg,/L, （18.8±2.8）μg/L, （22.4 ±4.1）μg/L, （16.4±2.3）μg/Land （12.1 ±l.6）μg/L, respectively. The level of vasoactive intestinal peptide of the SO group at postoperative 24 hours was significantly higher than that of the CO group （t = 3.59, P 〈 0.05 ） ; the levels of vasoactive intestinal peptide of the IR group at postoperative 24, 48 and 72 hours were significantly higher than those of the SO group （t = 6. 35,3.22, 2. 36, P 〈 0.05） ; the levels of vasoactive intestinal peptide of the SM group at postoperative 24 and 48 hours were significantly higher than those of the SO group （ t = 5. 04, 2. 33, P 〈 0.05 ）, while there was no significant difference in the level of vasoactive intestinal peptide between the SM group and the SO group at postoperative 72 hours （t = 0. 18 ,P 〉 0.05 ） ;the levels of vasoactive intestinal peptide of the SM group at postoperative 24, 48 and 72 hours were significantly lower than those of the IR group （t = 4. 27, 3.87, 2. 45, P 〈 0.05 ）. The level of secretin of the CO group was （75 ± 5 ） μg/L. The levels of secretin of the SO group, IR group and SM group at postoperative 24, 48 and72 hours were （98-±6）μg/L, （76±4）μg/L, （76 ±4）μg/L, （129 ±6）μg/L, （102± 8 ） μg/L, （ 89 ± 6 ） μg,/L, （ 104 ± 8 ） μg/L, （ 90 ± 6 ） μg/L and （ 74 ± 4 ） μg/L, respectively. The level of secretinof the SO group at postoperative 24 hours was significantly higher than that of the CO group （ t = 3.27, P 〈 O. 05 ） ; the levels of secretin of the IR group at postoperative 24, d and 72 hours were significantly higher than those of the SO group （t = 5. 20, 2. 94, 1.77, P 〈 0.05 ） ; the level of secretin of SM group at postoperative 24 and 48 hours were significantly higher than those of the SO group （t = 4. 16, 2. 54, P 〈 0.05）, while there was no significant difference in the level of secretin between the SM group and the SO group at postoperative 72 hours （ t = 0. 23,P 〉 0.05 ） ; the levels of secretin of the SM group at postoperative 24, 48 and 72 hours were significantly lower than those of the IR group （ t = 5. 13,4. 32,2. 87, P 〈 0.05 ）. Conclusions Gastrointestinal congestion caused by hepatic blocking leads to the decline of the expression of motilin, but the increase of the expression of cholecystokinin, vasoactive intestinal peptide, secretin. Salvia mihiorrhiza may improve micro-circulation, abate gastrointestinal adema, and influence the gastrointestinal hormone expression in an indirect way.