The Clinical And Experimental Research Of Xiaohuang Decotion On Chronic Hepatitis B Patients (Damp-heat Blood Stasis Syndrome) With Low-grade Jaundice

Part I The clinical research of Xiaohuang Decotion on chronic hepatitis B patients (damp-heat blood stasis syndrome) with low-grade jaundiceObjective:To evaluate the clinical efficacy of XHD on chronic hepatitis B patients (damp-heat blood stasis syndrome) with low-grade jaundice.Methods:71chronic hepatitis B patients (damp-heat blood stasis syndrome) with low-grade jaundice were simply randomly divided into two groups by random number table,40patients in treatment group and31in control group. Patients in both two groups received the same basic therapeutic regimen, lamivudine tablets100mg (or telbivudine tablets600mg) of taking orally once daily, compound glycyrrhizin injection60ml once daily, and reduced glutathione sodium for injection1.2g once daily. Base on the regimen above, patients in treatment group received XHD100ml, twice a day and patients in control group received UDCA250mg taking orally,3times a day. The treatment course was4weeks. And TCM clinical symptoms and signs, liver function, serum lipid, liver fibrosis index, and APRI index were evaluated before and after treatment course.Results:①The rate of symptoms and signs improvement in treatment group to chronic hepatitis B patients with low-grade jaundice was higher than control group (89.5%vs.76.7%), but not significantly (P>0.05).HD could improve liver function and serum lipid level (ALT,AST,y-GT,LDH,TBiL,DBiL,pre-A,TBA,TC, apo-A,HDL,etc) significantly compared to those before treatment (P<0.01or P<0.05). Compared to control group, XHD could reduce TBiL, DBiL, TBA and TC level, and elevate apo-A level effectively (P<0.05). On the contrary, XHD couldn’t improve the ALP,CHE,TP,Alb,G1b,TG,apo-B and LDL level significantly (P>0.05).③The hyaluronic acid (HA) level and precollagen iii peptide (PIIIP) level in both groups was lower than that before treatment (P<0.01), and the laminin (LN) and type IV collagen levels in treatment group were also lower than that before treatment (P<0.01). Compared to those in coontrol group, LN, PIIIP and C-IV levels of patients in treatment group were significantly improved (P<0.05).④The APRI index in treatment group was significantly reduced than that before treatment (P<0.01), and also was significant compared to that in control group (P<0.05).Conclusion:XHD could alleviate the clinical symptoms and signs of chronic hepatitis B patients (damp-heat blood stasis syndrome) with low-grade jaundice, improve the liver function, serum lipid and liver fibrosis index of these patients. And XHD could achieve a better therapeutic effect for intrahepatic cholestasis jaundice. Part II The experimental research of Xiaohuang Decotion on cholestasis jaundice in ANIT-induced ratsObjective:To evaluate the treatment efficacy and the anti-inflammation mechanism of Xiaohuang Decotion (XHD) on ANIT-induced intrahepatic cholestasis jaundice in Wistar rats.Methods:Male Wistar rats (40) were randomly divided into normal group (10) and ANIT-treated group (30). A single dose ANIT120mg/kg was given by gavage to rats treated by ANIT, and the same dose of ANIT was given every48h to ANIT-rats to produce a transient intrahepatic cholestasis. After ANIT treated48h, ANIT-treated group were randomly divided into model group, treatment group, and control group (10for each). ANIT-treated rats above were given normal saline, XHD and UDCA respectively for1week. At the end of the experiment all rats were sacrificed. General condition, liver function and liver histology of rats were examined. And we tested CD68factor by immunohistochemistry and Western blot, and detected CD68, TNF-a, IL-1β and IL-4by real-time PCR.Results:①Compared to rats in normal group, ALT, AST, ALP, TBiL, DBiL and TBA levels of rats in model group were significantly increased (P<0.01), and also Alb reduced (P<0.05), GIb increased significantly (P<0.05). Compared to rats in model group, XHD could significantly reduce ALT, AST, ALP, TBiL, DBiL and TBA levels of ANIT-treated rats (P<0.01or P<0.05). Also, UDCA could reduce TBiL, DBiL and TBA levels of ANIT-treated rats significantly (P<0.01or P<0.05). Unfortunately, UDCA had little improvement on ALT, AST and ALP levels of ANIT-treated rats (P>0.05).②Compared to model group, XHID alleviated inflammatory cell infiltration and inhibit hepatocellular necrosis of ANIT-treated rats effectively. UDCA could also improve the liver histology of ANIT-treated rats to some degree.③Liver histology immunohistochemistry of CD68showed that positive staining of CD68was enhanced obviously in rats in model group, compared to rats in normal group. Compared to rats in model group, positive staining of CD68was relieved evidently in rats both in treatment group and control group.④Liver histology Western blot results of CD68showed that CD68expression level of rats in normal group was low, which was increased significantly after ANIT treatment (P<0.01). Compared to model group, CD68level were significantly reduced by intervention of both XHD and UDCA (P<0.01).⑤Liver histology real-time PCR results showed that CD68, TNF-a and IL-1β of rats in model group were significantly increased, and IL-4was induced significantly after ANIT treatment (P<0.01or P<0.05). Compared to model group, CD68, TNF-a and IL-1β of rats in treatment group were significantly reduced and IL-4was significantly increased (P<0.01or P<0.05). UDCA could reduce CD68and TNF-a level, and improve IL-4expression of ANIT-treated rats significantly (P<0.01or P<0.05), though it could not reduce IL-1β significantly (P>0.05).Conclusion:XHD has good hepatoprotective and jaundice-relieving effects. Inflammation response mediated by Kupffer cells is the important pathological link of ANIT-induced intrahepatic cholestasis, and anti-inflammation might be one important mechanism for XHD in jaundice-relieving in ANIT-treated rats.