| ObjectiveTo study the effects and mechanism of YINCHENZELAN Decoction(YCZLD) onthe acute liver failure model in rats.Methods110 Wistar rats, weighed 180-220g, were randomly divided into six groups:normal control group (10 rats), ALF group (20 rats), YCZLD group of small dose(20 rats), YCZLD group of middle dose (20 rats), YCZLD group of high dose (20rats), pHGF group (20 rats). After being fasted overnight (over 14h), all rats (exceptthe normal control group) were injected with TAA 600mg.kg-1 twice with a gap of24h in between to induce the acute liver failure; the normal group was injected withthe 0.9% salt solution hypodermically. From the first administration of TAA to theend of experiment, each rat was injected with a mixture of solution containing 10%glucose 3ml, 1ml saline, and 1ml 20umol/L KCl every 8h to avoid hypoglycemia. Therats were treated respectively with the 0.9% normal saline, YCZLD low/middle/highdosages, or pHGF every day for 3 days.The mortality of the rats in 48 hours wasobserved; the blood were collected to measure liver function (serum ALT, AST, TBil),tumor necrosis factor-a (TNF-α) and Interletukin-6(IL-6) after TAA were injected inthe second time; and the hepatic tissues were collected immediately. The pathologicalmorphologies of hepatia tissues were observed under optical microscopes and themitosis indexes of hepatic cells were measured. The expression of PCNA, signalregulatory protein-a (SIRP-α.) in liver cells was detected immunohistochemically,and the expression of HMGBI mRNA, AQP-4 mRNA and CD14mRNA in liver wasexamined with reverse transcription polymerase chain reaction(RT-PCR).Results:1. YCZLD can decrease the mortality of the rats with ALF, as well as the indexesof liver function(ALT,AST, TB); and can ameliorate the ultrastructures of liver. Therewere significant differences when comparing YCZLD groups with the model andpHGF groups (P＜0.01 or P＜0.05).2. In the normal group, the mitosis indexes of hepatic cells and the expression ofPCNA were much lower comparing with those in the model group (P＜0.01). After treated with YCZLD and pHGF, the mitosis indexes of hepatic cells and theexpression of PCNA increased significantly comparing with those in the model group(P＜0.01), and they increased with the addition of the YCZLD dosage, as well.3. The expression of S1RPα1 in the model and pHGF groups increasedsignificantly comparing with that in the nomal group (P＜0.01). After treated withYCZLD, the expression of SIRPα1 increased significantly comparing with those inthe normal and model groups (P＜0.01), and increased with the addition of the dosage.4. The expression of the IL-6 and TNF-αon ALF model rats was higher than theother groups. After treated with YCZLD, the expression of TNF-αon ALF decreasedsignificantly comparing with those in the model group (P＜0.01) and decreased withthe addition of the dosage. The expression of TNF-αon AHF decreased significantlyin the middle and high YCZLD dose group comparing with those in the low group(P＜0.01). There were no significant differences between the low-dosage YCZLDtreated group and the pHGF group (P＞0.05).5. In the normal group, the expression of HMBG1 mRNA was low, and in ALFmodel group it was increased significantly (P＜0.01). After treated with YCZLD, theexpression of HMBG1 decreased significantly comparing with those in the modelgroup (P＜0.01) and decreased with the addition of the YCZLD dosage. Theexpression of HMBG1 mRNA decreased significantly in the middle and highYCZLD dose group comparing with those in the low dose group and pHGF group(P＜0.01).6. The expression of AQP4 mRNA was low in the normal group,while in AHFmodel group it was increased significantly (P＜0.01). After treated with YCZLD, theexpression of AQP4 mRNA in ALF model group decreased significantly, especiallyin the middle and high YCZLD dose group if compare with those in the low dosegroup and the pHGF group (P＜0.01).7. The expression of CD14 mRNA in the rat with acute hepatic failure wasresisted by YCZLD and also related to its dosage. After treated with YCZLD, theexpression of CD14mRNA decreased significantly(P＜0.01). The increase of CD14mRNA expression in the ALF group comparing with those in the normal group mayindicate that endotoxin contributed to ALF.Conclusion1. YCZLD can decrease the mortality of the ALF rats. It also can decrease theindexes of liver function(ALT, AST,Tbil), the TNF-α, IL-6, and the expression of CD14 mRNA, HMGB1 mRNA and AQP4 mRNA significantly comparing with thoseof model group. It showed that YCZLD can protect the liver from being damaged byTAA in certain degree.2. YCZLD can increase the mitosis indexes of hepatic cells and the expression ofPCNA, SIRPα1. It showed that YCZLD can promote the regeneration of liver.Andit seemed to be more effective when increase the YCZLD dosage. The middle andhigh dose group of YCZLD was superior to the low dose group.
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