Protective effects of baicalin and octreotide on multiple organ injury in severe acute pancreatitis.
OBJECTIVE
To discuss the application value of Baicalin which is a new drug by comparing the protecting effects of Baicalin and Octreotide on multiple organs (pancreas, liver, kidney, and lung) in Severe acute pancreatitis (SAP).


METHODS
The improved Aho method was adopted to prepare SAP rat models via retrograde injection of 3.5% sodium taurocholate to the pancreatic duct. The 135 SAP rat models after being prepared were randomly divided into the model group, Baicalin treatment group and Octreotide treatment group with 45 rats in each group; another 45 were selected to be the sham operation group, which only received abdomen opening surgery. The groups were then randomly divided into 3 h, 6 h and 12 h groups with 15 rats in each group, 10 min after successful modeling, the Baicalin treatment group was first injected with a 5% Baicalin injection at a dose of 10 mg/100 g via external jugular-vein passage followed by continuous intravenous administration (10 mg/h/100 g) by microinfusion pump; the Octreotide treatment group was first injected by Octreotide at a dose of 0.2 ug/100 g via external jugular-vein passage followed by continuous intravenous transfusion (10 mg/h/100 g) by microinfusion pump at a transfusion speed of 0.2 ug/h/100 g. The sham operation group and model group were injected with saline of equivalent volume at the corresponding time points after operation. The following observations were carried out 3, 6 and 12 h after operation: (1) mortalities of all rat groups followed by batch execution of rats and observation of the gross pathological changes of multiple organs; (2) observation of the pathological changes of multiple organ samples fixed according to the relevant requirements after HE staining; and (3) serum content of amylase, NO, malonaldehyde (MDA), and tumor necrosis factor alpha (TNF-alpha).


RESULTS
(1) The survival rate of the sham operation group and all treatment groups was 100%, whilst the 12 h survival of the model group was 66.67% (10/15), indicating a significant difference (P < 0.05). (2) The gross pathological changes and changes under light microscopy of multiple organs aggravated with time after modeling. The pathological changes of all treatment groups were milder than those of the model group at different time points by various degrees, most obviously at 6 h and 12 h. The gross pathological changes showed a similarity between the Octreotide and Baicalin treatment groups in terms of the pathological changes of pancreatic tissue. The therapeutic effects of Octreotide on kidney and lung were superior to those in the Baicalin treatment group while the pathological manifestations of the Baicalin treatment group were superior to those of the Octreotide treatment group. (3) There was no marked difference between the Baicalin and Octreotide treatment groups in terms of plasma amylase levels at all time points (P > 0.05). Although the plasma amylase levels of the Baicalin treatment group were lower than those of the model group at all time points, the levels in the Baicalin treatment group were significantly lower than those in the model group only at 3 h (P < 0.05), and there was no marked difference in the levels between the Baicalin treatment group and model groups at 6 and 12 h (P > 0.05); the levels in the Octreotide treatment group were significantly lower than in the model group at 6 h (P < 0.05), and there was no marked difference between the levels in the Octreotide treatment group and model group at 3 h and 12 h (P > 0.05). (4) The serum NO contents of the Baicalin treatment group were significantly lower than those of the model group (P < 0.05), while in the Octreotide treatment group it was obviously lower than in the model group at 3 and 12 h (P < 0.01); in this regard there was no marked difference between the Baicalin and Octreotide treatment groups at different time points (P > 0.05). (5) The serum MDA contents of the Baicalin treatment group were significantly lower than those of the model group (P < 0.01), while in the Octreotide treatment group it was significantly less than the model group at 6 and 12 h (P < 0.05), and in the Baicalin treatment group was significantly less than in the Octreotide treatment group at 12 h (P < 0.05). (6) There was no marked difference among the model group, Baicalin treatment group and Octreotide treatment group in terms of serum TNF-alpha content at 3 h and 12 h (P > 0.05). At 6 h the value in the Baicalin treatment group was significantly less than in the model group (P < 0.001), in the Octreotide treatment group it was significantly less than in the model group (P < 0.001), and the Octreotide treatment group it was significantly less than in the Baicalin treatment group (P < 0.01).


CONCLUSIONS
Both Baicalin and Octreotide have obvious protective effects on the multiple organ injury in SAP with mechanisms associated to manifold factors. By comparing the pharmacologic effects of Octreotide and Baicalin, we believe that Baicalin as a new drug has a protective effect on multiple organs of a SAP rat model similar to that of Octreotide and is worth further study and development.
Zhang
Xi Ping
XP
Department of General Surgery, Hangzhou First People's Hospital, 261 Huansha Road, Hangzhou, Zhejiang Province 310006, China. zxp99688@vip.163.com
Zhang
Ling
L
Yang
Ping
P
Zhang
Rui Ping
RP
Cheng
Qi Hui
QH
D000681:Amylases / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009102:Multiple Organ Failure / Q000517:prevention & control*; D009569:Nitric Oxide; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use*; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000150:complications* / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C038044:baicalin; D008315:Malondialdehyde; D000681:Amylases; D015282:Octreotide