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Purpose To explore the clinical and pathologi-cal features and the relationships between pathological features and drugs of patients with drug-induced liver injury(DILI)based on the hepatotoxicity injury patterns.Methods The clin-ical data,laboratory indicators,drugs,and liver biopsy of 50 cases of DILI were collected,the expression of CK19 was detec-ted by immunohistochemistry EnVision two-step method,and the reticular scaffold of liver tissue was displayed by Reticular fiber staining.Results Among the 50 patients with DILI,there were 29 cases of hepatocellular DILI,11 cases of cholestatic DILI,and 10 cases of mixed DILI,respectively,with the hepatocellu-lar DILI accounting for the highest proportion(58％).7 catego-ries of drugs induced DILI,with herbal ranking first(52％).Different types of drugs could cause different types of DILI,with herbal induced 17 cases hepatocellular DILI(58.62％)and an-ti-infectious and anticancer drugs induced all 3 cases cholestatic DILI(27.27％).Different types of DILI displayed various pathological characteristics.Hepatocellular congestion,feathery degeneration,and small bile duct thrombosis primarily occur in cholestasis and mixed DILI,while bridging necrosis,sub-large and large necrosis were mainly seen in hepatocellular DILI.Conclusion Based on hepatotoxicity injury patterns,DILI ex-hibits a variety of clinical and pathological characteristics,and there is some relationship between pathological characteristics and drugs.Liver puncture pathological biopsy plays an important role in improving the diagnosis and treatment of DILI.
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This study aims to observe the effect of chlorogenic acid(CGA) on microRNA(miRNA) in the process of protecting against N-acetyl-p-aminophenol(APAP)-induced liver injury. Eighteen C57BL/6 mice were randomly assigned into a normal group, a model group(APAP, 300 mg·kg~(-1)), and a CGA(40 mg·kg~(-1)) group. Hepatotoxicity of mice was induced by intragastric administration of APAP(300 mg·kg~(-1)). The mice in the CGA group were administrated with CGA(40 mg·kg~(-1)) by gavage 1 h after APAP administration. The mice were sacrificed 6 h after APAP administration, and plasma and liver tissue samples were collected for the determination of serum alanine/aspartate aminotransferase(ALT/AST) level and observation of liver histopathology, respectively. MiRNA array combined with real-time PCR was employed to discover important miRNAs. The target genes of miRNAs were predicted via miRWalk and TargetScan 7.2, verified by real-time PCR, and then subjected to functional annotation and signaling pathway enrichment. The results showed that CGA administration lowered the serum ALT/AST level elevated by APAP and alleviate the liver injury. Nine potential miRNAs were screened out from the microarray. The expression of miR-2137 and miR-451a in the liver tissue was verified by real-time PCR. The expression of miR-2137 and miR-451a was significantly up-regulated after APAP administration, and such up-regulated expression was significantly down-regulated after CGA administration, consistent with the array results. The target genes of miR-2137 and miR-451a were predicted and verified. Eleven target genes were involved in the process of CGA protecting against APAP-induced liver injury. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment with DAVID and R language showed that the 11 target genes were enriched in Rho protein-related signal transduction, vascular patterning-related biological processes, binding to transcription factors, and Rho guanyl-nucleotide exchange factor activity. The results indicated that miR-2137 and miR-451a played an important role in the inhibition of CGA on APAP-induced hepatotoxicity.
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Animals , Mice , Mice, Inbred C57BL , Chlorogenic Acid , Acetaminophen , Chemical and Drug Induced Liver Injury, Chronic , Alanine Transaminase , MicroRNAsABSTRACT
Objective To observe the indexes of liver injury and the expression of inflammation-related factor interleukin-10 (IL-10) in rats with severe acute pancreatitis (SAP), and to discuss the correlation between the expression of IL-10 and the related factors of liver injury in SAP rats at different altitudes. Methods 280 male Wistar rats with SPF grade aged 5 to 6 months were divided into four groups according to random number table with 70 rats in each group, and the rats were placed in different altitudes such as Xi'an (at an altitude of 1 027 m), Xining (at an altitude of 2 260 m), Xinghai (at an altitude of 3 300 m) and Wenquan (at an altitude of 3 950 m). The rats in each altitude were randomly divided into sham operation group (Sham group, n = 10) and SAP 1, 6, 12, 24 hours groups (all n = 15). SAP rat model was reproduced by injecting sodium cholate into the posterior membrane of pancreas, and the rats of Sham group were only turned pancreas over several times after opening the abdomen and then closed the abdomen. The rats were sacrificed at the corresponding time points after model reproduction in SAP groups, and rats in Sham group were sacrificed at 6 hours after sham operation. At the same time, the abdominal aorta blood was harvested, and the contents of serum amylase (AMY), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined by automatic biochemical analyzer. Liver tissues were harvested, and the expression level of IL-10 was determined by immunohistochemistry. Pancreatic tissues were harvested, and hematoxylin-eosin (HE) staining was performed to observe the pathological changes under light microscopy. The correlations among the indicators were analyzed by Pearson correlation. Results At different altitudes, no significant abnormality was found in the pancreas of Sham group, but significant pathological changes were found in the pancreas of all SAP groups, mainly manifested as pancreatic acinar swelling, inflammatory cell infiltration, vascular congestion and hemorrhage, acinar cell degeneration and dissolution, changes in glandular lobule structure, peri-pancreatic fat necrosis, and continuous aggravation with the increasing of time and altitude. At the same altitude, the pancreatic pathology score, the serum AMY, ALT and AST levels, and the hepatic IL-10 expression were all significantly increased in all the SAP groups as compared with those in Sham group, and they were continuously increased with time. In Sham group, there was no statistically significant difference in pancreatic pathology score, AMY, ALT, AST, or IL-10 level among different altitudes. At the corresponding time point after model reproduction, the pancreatic pathology score, AMY, ALT, AST and IL-10 levels in the SAP groups were also shown a continuous rising tendency with altitude increase, and the differences in above parameters of SAP 24 hours group in Wenquan area were statistically significant as compared with those of Sham group [pathology score: 11.06±0.94 vs. 0.23±0.15, AMY (mmol/L): 2 706.6±208.3 vs. 336.5±94.3, ALT (U/L): 267.00±5.37 vs. 52.00±4.84, AST (U/L): 465.88±11.02 vs. 139.00±11.61, IL-10 (A value): 0.579±0.006 vs. 0.281±0.006, all P < 0.05]. It was shown by correlation analysis that IL-10 of SAP rats at different altitudes was positively correlated with pancreatic pathology score, AMY, ALT and AST, the correlation coefficient (r value) between IL-10 and the above indicators in the Wenquan area with the highest altitude was 0.959, 0.928, 0.977, 0.983, respectively (all P < 0.01). Conclusions The severity of SAP rats was positively correlated with altitude. IL-10 was involved in the pathological expression process of SAP liver damage, and its expression level was positively correlated with altitude and the degree of SAP liver damage.
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OBJECTIVE: To prepare total lignans of Herpetospermumcaudigerum nanosuspension capsules (NSC), and study its hepatoprotective effect against acute live injury induced by carbon tetrachloride (CC14) in comparison with Ganneng dripping pills. METHODS: TL-NS was prepared by high pressure homogenization technique, and characterized in terms of morphology and particle size et al. The serum levels of ALT and AST and the activities of SOD and MDA in liver tissue homogenates were measured in the rat model of acute liver injury induced by intraperitoneal injection of 30% CC14, and the hepatic pathological morphology was observed by optical microscope. RESULTS: After being dissolved, NSC was irregular spheroidal as observed by scanning electron microscopy, and the other quantitative values of physical and chemical characterization were within reasonable ranges. Compared with Ganneng dripping pils, the levels of ALT, AST and MDA of the rats treated with NSC were significantly lowered, and the activities of SOD in liver tissue was increased obviously. Histological observation showed that NSC could ameliorate the histological damages induced by CC14. CONCLUSION: The hepatoprotective effects of NSC are significantly better than Ganneng dripping pils. This study provides certain reference to the dosage form development and clinical application of total lignans.
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Objective:To evaluate the efficacy and safety of deoxyribonucleotide in intervention with solid tumor. Methods:A exper-imental study and randomized clinical trial were conducted. Experimental study part: MTT assay and S-180 sarcoma method were launched to observe whether the deoxyribonucleotide would affect the tumor growth. Clinical study part:86 patients of lung cancer, gastric cancer, colorectal cancer, liver cancer were divided into control group(n=43) and treatment group (n=43). Both group were given routine therapy,and the treatment group were given deoxyribonucleotide at the same time. Bone marrow suppression and live function were assessed after chemotherapy. Results:Chemotherapy Clinical effect did not improved in Deoxyribonucleotide group (47. 5% vs 44. 9%, P>0. 05), however, theⅢ-Ⅳbone,NKcellswere improved by deoxyribonucleotide (P<0. 05). What is more, the live injury of treat-ment group were less than the control group. Conclusion:Deoxyribonucleotide can decrese the occurace rate of live injury and bone mar-row suppression.