辽宁中医药大学学报

目的 研究大柴胡汤合苓桂术甘汤对高脂血症性急性胰腺炎大鼠内质网应激反应蛋白GRP78表达的影响，并研究其作用机制。方法 将72只健康成年SD大鼠分为6组2批次，分别为空白对照组，高脂血症性急性胰腺炎组，中药（大柴胡汤合苓桂术甘汤）低、中、高剂量治疗组，西药治疗组，每组6只SD大鼠。造模方式选用高脂饮食喂养14 d后雨蛙肽注射诱导高脂血症性急性胰腺炎，验证造模成功后，大柴胡汤合苓桂术甘汤低、中、高剂量治疗组和西药治疗组立普妥、抗生素头孢克肟灌胃、股静脉注入奥曲肽；空白对照组和疾病模型组给予等剂量生理盐水灌胃。首批次大鼠在给药后3 d，运用酶联免疫吸附测定法ELISA检测法测定血清淀粉酶（serum amylase,AMY）、血脂肪酶（blood lipase,LPS）的含量，运用全自动生化分析仪对游离脂肪酸（free fatty acid,FFA）进行检测，后将大鼠麻醉处死，对大鼠胰腺标本进行采样，运用Western blot检测法对大鼠胰腺组织中内质网应激反应蛋白GRP78表达进行测定。给药7 d后再采用全自动生化分析仪对甘油三酯（triglyceride,TG）、谷丙转氨酶（alanine aminotransferase,ALT）、谷草转氨酶（aspartate transaminase,AST）、肌酐（creatinine,CREA）、尿素氮（blood usea nitrogen,BUN）、肾小球滤过率（glomerular filtration rate,GFR）进行检测，最后应用SPSS 27.0软件将检测结果建立数据库并对计量数据资料进行统计学分析。结果 给药3 d后：大柴胡汤合苓桂术甘汤低剂量组、大柴胡汤合苓桂术甘汤中剂量组、大柴胡汤合苓桂术甘汤高剂量组、西药组大鼠AMY、LPS、FFA水平均低于高脂血症性急性胰腺炎组，差异有统计学意义（P<0.05）；大柴胡汤合苓桂术甘汤高剂量组大鼠AMY、LPS、FFA水平低于西药组，差异有统计学意义（P<0.05）；大柴胡汤合苓桂术甘汤高剂量大鼠AMY、LPS、FFA水平低于大柴胡汤合苓桂术甘汤低剂量组、大柴胡汤合苓桂术甘汤中剂量组，差异有统计学意义（P<0.05）；给药7 d后：大柴胡汤合苓桂术甘汤低剂量组、大柴胡汤合苓桂术甘汤中剂量组、大柴胡汤合苓桂术甘汤高剂量组、西药组大鼠TG水平均低于高脂血症性急性胰腺炎组，差异有统计学意义（P<0.05）；大柴胡汤合苓桂术甘汤高剂量组大鼠TG水平低于西药组，差异有统计学意义（P<0.05）；大柴胡汤合苓桂术甘汤高剂量大鼠TG水平低于大柴胡汤合苓桂术甘汤低剂量组、大柴胡汤合苓桂术甘汤中剂量组，差异有统计学意义（P<0.05）;Western blot检测GRP78表达量大柴胡汤合苓桂术甘汤低剂量组、大柴胡汤合苓桂术甘汤中剂量组、大柴胡汤合苓桂术甘汤高剂量组、西药组均低于高脂血症性急性胰腺炎组，差异有统计学意义（P<0.05），且大柴胡汤合苓桂术甘汤高剂量组抑制作用高于西医组，差异有统计学意义（P<0.05）。结论 大柴胡汤合苓桂术甘汤可以有效降低HLAP大鼠体内AMY、LPS、FFA、TG、GRP78含量，降低脂毒性，从而减轻内质网应激反应，降低GRP78的表达。

Objective To investigate the effect of Dachaihu Decoction and Lingguizhugan Decoction（大柴胡汤合苓桂术甘汤）on the expression of endoplasmic reticulum stress response protein GRP78 in rats with hyperlipidemic acute pancreatitis,and to study its mechanism of action. Methods 72 healthy adult SD rats were divided into 6 groups,respectively blank control group,HLAP,TCM different dose treatment group,TCM(Dachaihu Decoction and Linggui Zhugan Decoction) low,medium and high dose treatment group,Western medicine treatment group,6 SD rats in each group. The modeling method was selected to induce hyperlipidemic acute pancreatitis by injection of rain frog peptide after feeding on high fat diet for 14 days. After the successful modeling,the low,medium and high dose treatment group of Dachaihu Decoction and Linggui Zhugan Decoction and the Western medicine treatment group were given Lipitor,antibiotic cefixime and octreotide by gavage;the blank control group and the disease model group were given the same dose of normal saline by gavage. The first batch of rats were given 3 days after the drug,the contents of serum amylase(AMY)and blood lipase(LPS)were determined by enzyme-linked immunosorbent assay(ELISA),and the free fatty acid(FFA)was detected by automatic biochemical analyzer. After the rats were anesthetized and executed,the pancreatic specimens were sampled,and the expression of endoplasmic reticulum stress response protein GRP78 in the pancreatic tissue of rats was determined by Western blot detection method. After 7 days of administration,TG,alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(CREA),blood urea nitrogen(BUN),and glomerular filtration rate(GFR)were detected by automatic biochemical analyzer. Finally,the test results were analyzed by using SPSS27.0 software to establish a database and statistically analyze the measurement data. Results After 3 days of administration,the levels of AMY,LPS and FFA in the D+L low group,D+L medium group,D+L high group and the Western medicine group were lower than those in the HLAP group,and the differences were statistically significant(P<0.05). The levels of AMY,LPS and FFA in the D+L high group were lower than those in the western medication group,and the differences were statistically significant(P<0.05). The levels of AMY,LPS and FFA in D+L high group were lower than those in D+L low group and D+L medium group,and the differences were statistically significant(P<0.05). After 7 days of administration,the TG levels of rats in the D+L low group,D+L medium group,D+L high group and Western medicine group were lower than those in the HLAP group,and the difference was statistically significant(P<0.05). The TG level of the D+L high group was lower than that of the Western medicine group,and the difference was statistically significant(P<0.05). The TG level of D+L high group was lower than that of D+L low group and D+L middle group,and the difference was statistically significant(P<0.05). Western blot showed that the expression of GRP78 in the low D+L group,the middle D+L group,the high D+L group and the Western medicine group was lower than that in the HLAP group,and the difference was statistically significant(P<0.05). The inhibitory effect of the high D+L group was higher than that of the Western medicine group,and the difference was statistically significant(P<0.05). Conclusion Dachaihu Decoction and Linggui Zhugan Decoction can effectively decrease the expression of AMY,LPS,FFA,TG,and GRP78 in HLAP rats,reduce lipotoxicity,thereby reducing endoplasmic reticulum stress response and reducing the expression of GRP78.