Inhibitory effect of roburic acid in combination with docetaxel on human prostate cancer cells.

Roburic acid (ROB) is a naturally occurred tetracyclic triterpenoid, and the anticancer activity of this compound has not been reported. Docetaxel (DOC) is the first-line chemotherapeutic agent for advanced stage prostate cancer but toxic side effects and drug resistance limit its clinical success. In this study, the potential synergistic anticancer effect and the underlying mechanisms of ROB in combination with DOC on prostate cancer were investigated. The results showed that ROB and DOC in combination synergistically inhibited the growth of prostate cancer cells. The combination also strongly induced apoptosis, and suppressed cell migration, invasion and sphere formation. Mechanistic study showed that the combined effects of ROB and DOC on prostate cancer cells were associated with inhibition of NF-κB activation, down regulation of Bcl-2 and up regulation of Bax. Knockdown of NF-κB by small interfering RNA (siRNA) significantly decreased the combined effect of ROB and DOC. Moreover, we found that esomeprazole (ESOM), a proton pump inhibitor (PPI), strongly enhanced the effectiveness of ROB and DOC on prostate cancer cells in acidic culture medium. Since acidic micro environment is known to impair the efficacy of current anticancer therapies, ESOM combined with ROB and DOC may be an effective approach for improving the treatment of prostate cancer patients.

Using Case Costing to Evaluate the Potential Impact of a Reintegration Unit on an Acute-Care Hospital's Capacity and Resources.

The Ontario Ministry of Health funded a reintegration unit to transition hospitalized patients who no longer required acute care to alternate level of care (ALC), such as long-term care. In its first year, 102 (3.5%) patients of the hospital's waiting-for-ALC population were transferred, with 37.3% transferred on the day of ALC readiness. The reintegration unit reduced direct hospital costs by $861,000. Using case costing, we modelled optimized scenarios including all transfers on the day of ALC readiness and increased transfers to the reintegration unit; this helped reduce avoided direct costs by $2.3-$5.4 million. Acute-care bed capacity could have increased by 11%. We outline strategies to optimize future performance of the reintegration unit.

Synthesis and structure-activity relationships of 5-phenyloxazole-2-carboxylic acid derivatives as novel inhibitors of tubulin polymerization.

A series of 5-phenyloxazole-2-carboxylic acid derivatives were synthesized, and their structure-activity relationships (SARs) were studied. N,5-diphenyloxazole-2-carboxamides 6, 7, and 9, which mimicked ABT751, showed improved cytotoxicity compared with ABT751. Compound 9 exhibited the highest antiproliferative activities against Hela A549, and HepG2 cancer cell lines, with IC50 values of 0.78, 1.08, and 1.27 µM, respectively. Furthermore, compound 9 showed selectivity for human cancer cells over normal cells, and this selectivity was greater than those of ABT751 and colchicine. Preliminary mechanism studies suggested that compound 9 inhibited tubulin polymerization and led to cell cycle arrest at G2/M phase. Molecular docking studies indicated that compound 9 bound to the colchicine binding site of tubulin. Our findings provided insights into useful SARs for further structural modification of inhibitors of tubulin polymerization.

Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways.

BACKGROUND: TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, can selectively kill cancer cells with little or no cytotoxicity toward normal human cells and is regarded as a potential relatively safe antitumor drug. However, some cancer cells are resistant to TRAIL-induced apoptosis. Thus, reagents that potentiate TRAIL-induced cytotoxicity are needed. Herein, we investigated whether shikonin, a natural compound from the root of Lithospermum erythrorhizon, can sensitize TRAIL-resistant cells to TRAIL-induced cytotoxicity. RESULTS: The viability of A549 cells, which were resistant to TRAIL, was significantly decreased after treatment with TRAIL followed by shikonin. The underlying mechanisms by which shikonin sensitizes cells to TRAIL-induced cytotoxicity were also examined. Combined treatment with shikonin and TRAIL activated the caspase and JNK pathways, inhibited the STAT3 and AKT pathways, downregulated the expression of Mcl-1, Bcl-2, Bcl-xL, c-FLIP and XIAP and upregulated the expression of Bid. CONCLUSIONS: In conclusion, the results indicated that shikonin sensitized resistant cancer cells to TRAIL-induced cytotoxicity via the modulation of the JNK, STAT3 and AKT pathways, the downregulation of antiapoptotic proteins and the upregulation of proapoptotic proteins.

Clinical, Biochemical, and Genetic Findings of Cystinuria in Chinese Children.

BACKGROUND: Cystinuria is a rare inherited renal stone disease caused by mutations in the SLC3A1 and SLC7A9 genes. The Chinese cystinuria phenotype and genotype have rarely been reported in the literature. METHODS: For this research, the clinical features and genetic etiology were analyzed in seven children, and the clinical characteristics were summarized. The blood and urine amino acids and acylcarnitine were analyzed. Additionally, the whole coding sequence and exon-intron junctions of the SLC3A1 and SLC7A9 genes were analyzed. RESULTS: These seven patients with cystinuria were from seven unrelated Chinese families, and they were diagnosed between the ages of 1 month and 16 years old. The urinary amino acids, including ornithine, arginine, and threonine, were elevated in these patients. A homozygous c.325G>A mutation in SLC7A9 was identified in two patients, and six SLC3A1 mutations were found in five patients. CONCLUSIONS: The core pedigree analysis showed that most of the parents carried mutations; however, there was no association between the clinical course and the genotype.

[Progress of gene editing technologies and prospect in traditional Chinese medicine].

Gene editing is a kind of technologies that makes precise modification to the genome. It can be used to knock out/in and replace the specific DNA fragment, and make accurate gene editing on the genome level. The essence of the technique is the DNA sequence change with use of non homologous end link repair and homologous recombination repair, combined with specific DNA target recognition and endonuclease.This technology has wide range of development prospects and high application value in terms of scientific research, agriculture, medical treatment and other fields. In the field of gene therapy, gene editing technology has achieved cross-time success in cancers such as leukemia, genetic disorders such as hemophilia, thalassemia, multiple muscle nutritional disorders and retrovirus associated infectious diseases such as AIDS and other diseases. The preparation work for new experimental methods and animal models combined with gene editing technology is under rapid development and improvement. Laboratories around the world have also applied gene editing technique in prevention of malaria, organ transplantation, biological pharmaceuticals, agricultural breeding improvement, resurrection of extinct species, and other research areas. This paper summarizes the application and development status of gene editing technique in the above fields, and also preliminarily explores the potential application prospect of the technology in the field of traditional Chinese medicine, and discusses the present controversy and thoughts.

Total synthesis and cytotoxic activities of longamide B, longamide B methyl ester, hanishin, and their analogues.

The marine alkaloids, longamide B (1), longamide B methyl ester (2), hanishin (3), and a series of non-naturally occurring analogues were synthesized in an efficient manner from inexpensive commercially available dl-aspartic acid dimethyl ester. The cytotoxicities of these natural products (1-3) and their analogues (9-15) were evaluated against human lung adenocarcinoma (A549) and human prostate cancer (PC3) cells. This is the first evaluation of the cytotoxicities of these alkaloids in these cancer cell lines and it revealed that analogue 15 had comparable cytotoxic activity to its natural parent compound, (±)-hanishin (3). This study provides useful information for further structural modification of these alkaloids in order to develop novel antitumor agents.

Synthesis and Biological Evaluation of Novel Resveratrol-NSAID Derivatives as Anti-inflammatory Agents.

Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may cause serious side effects such as gastric mucosal damage. Resveratrol, a naturally dietary polyphenol, exhibited anti-inflammatory activity and a protective effect against gastric mucosa damage induced by NSAIDs. In this regard, we synthesized a series of resveratrol-based NSAIDs derivatives and evaluated their anti-inflammatory activity against nitric oxide (NO) overproduction in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We identified mono-substituted resveratrol-ibuprofen combination 21 as the most potent anti-inflammatory agent, which is more active than a physical mixture of ibuprofen and resveratrol, individual ibuprofen, or individual resveratrol. In addition, compound 21 exerted potent inhibitory effects on the LPS-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Furthermore, compound 21 significantly increased the survival rate in an LPS-induced acute inflammatory model and produced markedly less gastric damage than ibuprofen. It was found that compound 21 may be a potent anti-inflammatory agent for the treatment of inflammation-related diseases.

[Methylenetetrahydrofolate reductase deficiency-induced schizophrenia in a school-age boy].

Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. It is known that MTHFR deficiency may result in hyperhomocysteinemia, but MTHFR deficiency-induced schizophrenia has been rarely reported. Here we present the clinical course, biochemical and genetic characteristics of schizophrenia resulted from MTHFR deficiency in a school-age boy. He was 13 years old. He was admitted with a two-year history of fear, auditory hallucination, learning difficulty, sleeping problems, irascibility, drowsing and giggling. At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine. Further DNA sequencing analysis showed 665C>T homozygous mutations in the MTHFR gene. The patient was diagnosed with MTHFR deficiency-associated schizophrenia and treatment with calcium folinate, vitamin B12, vitamin B6, and betaine was initiated. After the treatment for 1 week, his plasma and urine levels of homocysteine were decreased to a normal range and the clinical symptoms were significantly improved. After 3 months of treatment, the patient returned to school. He is now living with normal school life. In summary, children with late-onset MTHFR deficiency and secondary cerebral folate deficiency may lead to schizophrenia. This rare condition can be early diagnosed through analyses of blood and urine total homocysteine, amino acids in blood and folate in blood and cerebral fluid and successfully treated with folinic acid, vitamin B6, vitamin B12 and betaine.

Structural investigation and biological activity of sesquiterpene lactones from the traditional Chinese herb Inula racemosa.

Five new sesquiterpene lactones, racemosalactones A-E (1-5), along with 19 known sesquiterpene latones (6-24), were isolated from the roots of Inula racemosa. Their structures were elucidated by extensive spectroscopic analysis, and the absolute configuration of 2 was deduced from X-ray diffraction analysis. Compounds 1, 6, 8, 10, 12, 14, and 17 exhibited antiproliferative activities with IC50 values ranging from 0.38 to 4.19 µg/mL against human non-small-cell lung cancer A549, hepatocellular carcinoma HepG2, and human fibrosarcoma HT1080 cells. Compounds 6 and 8 exhibited antiproliferative activities against endothelial cells with IC50 values of 2.4 and 2.5 µg/mL, respectively. Furthermore, compounds 6 and 8 both inhibited endothelial cell tube formation at 1.0 µg/mL. A method for the rapid and straightforward preparative-scale isolation of compound 6 from alantolides is described.

[A boy with Fabry disease with the onset at the age of four].

Fabry disease is an X-linked recessive lysosomal storage disorder caused by a deficiency of α-galactosidase A (GLA). Intracellular accumulation of globotriaosylceramide, the glycolipid substrate of this enzyme, leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction. Patients of severe cases die young. It has been proved that enzyme replacement therapy is a useful method to treat patients with Fabry disease. But the clinical diagnosis of the patients may often be difficult because of the lack of specific symptoms. In this study, a Chinese boy was diagnosed as Fabry disease at the age of 11 years with episodic pain for 7 years. The boy described the onset, at the age of 4 years, of episodic burning pain in the toes. Generalized aching and pain in the feet became progressive in the past two years and his hands were also affected. Divers analgesics were tried without effects. When he was admitted at the age of 11 years, none of complications was found in his heart, brain, kidneys, skin and eyes by routine laboratory examinations. Significantly decreased GLA activity of peripheral leucocytes [1.0 nmol/(h×mg protein) vs. normal control 24.5 to 86.1 nmol/(h×mg protein)] supported the diagnosis of Fabry disease. A splicing mutation IVS6+2 T>C was identified on his GLA gene. But it was not found in his mother and younger sister. The incidence of Fabry disease is not clear in Mainland China. The patients usually have insidious onset with complex and non-specific clinical manifestations. Stroke, uremia, cardiomyopathy and multiple organ dysfunctions are common at the late stage. Early diagnosis is the key point to reduce the mortality and handicap. GLA enzyme activity is important to the diagnosis of Fabry disease. The mutation analysis of GLA gene is helpful for genetic counseling.

Structure and anti-inflammatory activity of neo-clerodane diterpenoids from Scutellaria barbata.

Herein, 13 previously undescribed neo-clerodane diterpenoids (1-13) and 27 known analogs (14-40) were isolated from the aerial parts of Scutellaria barbata. Absolute configurations of undescribed compounds were assigned based on single-crystal X-ray diffraction analysis and comparison of experimental and circular dichroism. All isolates were evaluated for the inhibition of nitric oxide generation induced by lipopolysaccharide in RAW 264.7 macrophages. Compound 36 was found to be the most active with an IC50 value of 10.6 µM. Structure-activity relations of these neo-clerodane diterpenoids revealed that the α, ß-unsaturated-γ-lactone moiety with an exocyclic conjugated double bond was necessary for maintaining and increasing its activity. Further mechanistic studies show that compound 36 suppressed nitric oxide synthase enzymes (iNOS) expression without affecting iNOS activity. Additionally, compound 36 suppresses NF-κB signaling by inhibiting IκBα phosphorylation.

Nitrovin (difurazone), an antibacterial growth promoter, induces ROS-mediated paraptosis-like cell death by targeting thioredoxin reductase 1 (TrxR1).

Glioblastoma multiforme (GBM) is one of the most lethal malignant tumors in the human brain, with only a few chemotherapeutic drugs available after surgery. Nitrovin (difurazone) is widely used as an antibacterial growth promoter in livestock. Here, we reported that nitrovin might be a potential anticancer lead. Nitrovin showed significant cytotoxicity to a panel of cancer cell lines. Nitrovin induced cytoplasmic vacuolation, reactive oxygen species (ROS) generation, MAPK activation, and Alix inhibition but had no effect on caspase-3 cleavage and activity, suggesting paraptosis activation. Nitrovin-induced cell death of GBM cells was significantly reversed by cycloheximide (CHX), N-acetyl-l-cysteine (NAC), glutathione (GSH), and thioredoxin reductase 1 (TrxR1) overexpression. Vitamins C and E, inhibitors of pan-caspase, MAPKs, and endoplasmic reticulum (ER) stress failed to do so. Nitrovin-triggered cytoplasmic vacuolation was reversed by CHX, NAC, GSH, and TrxR1 overexpression but not by Alix overexpression. Furthermore, nitrovin interacted with TrxR1 and significantly inhibited its activity. In addition, nitrovin showed a significant anticancer effect in a zebrafish xenograft model, which was reversed by NAC. In conclusion, our results showed that nitrovin induced non-apoptotic and paraptosis-like cell death mediated by ROS through targeting TrxR1. Nitrovin might be a promising anticancer lead for further development.

Comparison of the effects of carbamyl-beta-methylcholine chloride administered by intravenous, intramuscular and intra-acupuncture point injections.

OBJECTIVE: To compare the effects of carbamyl-beta-methylcholine chloride (CMCC) administered by intra-acupuncture point injection (IAI), intramuscular injection (IMI), and intravenous injection (IVI), and to analyze the mechanisms. METHODS: In the IAI group, CMCC was injected into the Zusanli acupoint (ST 36) immediately after 30-min stimulation by electro-acupuncture (EA) at the acupoints, and into the femoral vein and skeletal muscle in IVI and IMI groups, respectively. Intra-gastric pressure was detected. The plasma concentration of CMCC was measured at various times. RESULTS: The gastric effect of CMCC in the IVI group was enhanced and attenuated more rapidly than in the other groups. In the IAI group, this effect was significantly stronger than that in the IMI group at 2 min and 15 min, but not significantly different between the two groups at 5 min and 30 min. Plasma concentration of CMCC in the IAI group was similar to that in the IVI group at 2 min, but higher than that in the IMI group. The concentration in the IAI group was higher than that in the IV group and similar to that in the IMI group at 5, 15 and 30 min, indicating rapid increase and slower reduction of the plasma concentration of the drug in the IAI group. There was a positive correlation between the plasma concentration of CMCC and intragastric pressure in all groups. CONCLUSION: The effect of IAI with CMCC was stronger than that of IMI and longer-lasting than that of IVI, which correlated with the blood concentration of CMCC.

[Mitochondrial respiratory chain complex â ¡ deficiency and diseases].

This article reviews the structure and function of mitochondrial respiratory chain complex Ⅱ, and the clinical features, diagnosis, treatment and genetic analysis of mitochondrial respiratory chain complex Ⅱ deficiency. Mitochondrial complex Ⅱ, known as succinate dehydrogenase, is a part of the mitochondrial respiratory chain. It plays an important role in cellular oxidative phosphorylation. It is associated with oxidative stress and is a sensitive target for toxic substances and abnormal metabolin in cells. Clinical manifestations of respiratory chain complex Ⅱ deficiency are characterized by a wide variety of abnormalities. Progressive neuromuscular dysfunction is the most common syndrome. Cardiomyopathy, episodic vomit and hemolytic uremic syndrome are also encountered in a few cases. A precise diagnosis is dependent on enzyme activities assay of respiratory chain complexes and genetic analysis. Complex Ⅱ activities decreased in affected tissues. Pathogenic mutations in SDHA gene and SDHAF1 gene encoding assembly factor have been found so far. Clinical treatment aims at improving the mitochondrial function.

[Intrahepatic cholestasis due to mitochondrial respiratory chain complex I deficiency in a Chinese boy].

Mitochondrial respiratory chain deficiency is a common cause of mitochondrial disease in children. This study aimed to review the clinical, enzymatic and genetic characteristics of a Chinese boy with progressive intrahepatic cholestasis due to mitochondrial respiratory chain complex I deficiency. The boy developed diarrhea from the age of 13 months, followed by progressive body weight loss, jaundice and weakness. His urine organic acids, blood amino acids and acylcarnitines profiles were normal. Mitochondrial respiratory chain complexes I to V activities in peripheral leukocytes were measured using spectrophotometric assay. Complex I activity was reduced. 5821G>A mutation was indentified by gene sequencing on tRNA-cys of mitochondrial gene in the patient and his mother. Vitamin supplements, liver protection, antibiotics and plasma infusion were not effective in the patient. Unfortunately, the boy died at the age of 17 months. Mitochondrial respiratory chain complex I deficiency is the most common mitochondrial respiratory chain disorder. This was the first case of intrahepatic cholestasis due to complex I deficiency confirmed by mitochondrial respiratory chain enzyme activity assay and gene analysis in China. It was concluded that mitochondrial hepatopathy is one of major causes of metabolic hepatopathy. Biochemical assay, mitochondrial respiratory chain complex activities assay and genetic analysis are crucial for the etiological diagnosis of metabolic hepatopathy.

[Mitochondrial respiratory chain complex I deficiency due to 10191T>C mutation in ND3 gene].

This study reviews a case of mitochondrial respiratory chain complex I deficiency due to the 10191T>C mutation in mitochondrial ND3 gene. The previously healthy boy progressively presented with blepharoptosis, weakness, epilepsy and motor regression at age 6 years. Elevated blood lactate and pyruvate were observed. Brain magnetic resonance imaging showed symmetrical lesions in the basal ganglia. Leigh syndrome was thus confirmed. The protein from the mitochondria and genomic DNA of the boy and his parents was collected from peripheral blood leucocytes for the activity test for mitochondrial complex I to V and genetic analysis. The results showed the activity of complex I (33.1 nmol /min in 1 milligram mitochondrial protein) was lower than normal reference value (44.0±5.4 nmol /min in 1 milligram mitochondrial protein). The ratio of complex I to citrate synthase (19.8%) was also lower than normal reference value (48%±11%). The activities of complexes II to V were normal. 10191T>C mutation in ND3 gene of mitochondria was identified in the boy. 10191T>C mutation and complex I deficiency were not detected in his parents. At present, he is 16 years old, and of normal intelligence with spastic paralysis in both lower extremities after treatment. It is concluded that a Chinese boy with isolated complex I deficiency due to 10191T>C mutation in ND3 gene was firstly diagnosed by peripheral leukocytes mitochondrial respiratory chain enzyme assay and gene analysis. This study can provide clinical data for the nosogenesis of Leigh syndrome.

Synthesis and anticancer activity of novel histone deacetylase inhibitors that inhibit autophagy and induce apoptosis.

The combination of histone deacetylase (HDAC) and autophagy inhibitor has been considered as a novel cancer therapeutic strategy. To find novel HDAC inhibitors that can inhibit autophagy, several new series of oxazole- and thiazole-based HDAC inhibitors were designed and synthesized by replacing the phenyl cap in SAHA with 5-phenyloxazoles and 5-phenylthiazoles. The representative oxazole derivative, compound 21, showed better enzymatic inhibitory activity than SAHA (vorinostat). Compound 21 induced G2/M cell cycle arrest and its antiproliferative activity is 10-fold better than SAHA in multiple tumor cell lines. Western blot analysis showed that compound 21 can markedly increase the acetylation levels of tubulin, histone H3, and histone H4. Contrary to SAHA, compound 21 was found to inhibit autophagy. Additionally, compound 21 induced cell apoptosis via the Bax/Bcl-2 and caspase-3 pathways. Ultimately, compound 21 exhibited higher oral antitumor potency than SAHA in a A549 xenograft model. Our results indicated that compound 21 may be further developed as a promising anticancer agent.

Alteration of gut microbiota in high-fat diet-induced obese mice using carnosic acid from rosemary.

Rosmarinus officinalis (rosemary) is widely used as a food ingredient. Rosemary extract (containing 40% carnosic acid) exhibited potent antiobesity activity. However, the relationship between carnosic acid (CA) and changes in the gut microbiota of high-fat diet (HFD)-induced obese mice has not been fully investigated. C57BL/6 mice were fed a normal diet, an HFD, or an HFD containing 0.1% or 0.2% CA for 10 weeks. CA exhibited promising antiobesity effects and caused marked alterations in the gut microbiota of HFD-induced obese mice. CA caused the prevalence of probiotics and functional bacteria, including Akkermansia muciniphila, Muribaculaceae unclassified, and Clostridium innocuum group, and inhibited diabetes-sensitive bacteria, including Proteobacteria and Firmicutes. The ratio of Firmicutes to Bacteroidetes was regulated by CA in a dose-dependent manner, decreasing it from 13.22% to 2.42%. Additionally, CA reduced bile acid-metabolizing bacteria, such as Bilophila, Clostridium, Lactobacillus, and Leuconostoc. The results of the linear discriminant analysis and effect size analysis indicated that CA attenuated the microbial changes caused by HFD. The high CA (HCA) group (HFD containing 0.2% CA) exhibited a greater abundance of Verrucomicrobiae (including Akkermansia muciniphila, genus Akkermansia, family Akkermansiaceae, and order Verrucomicrobiales), Eubacterium, and Erysipelatoclostridium, and the low CA (LCA) group (HFD containing 0.1% CA) exhibited a greater abundance of Eisenbergiella, Intestinimonas, and Ruminococcaceae. Our results demonstrate that the antiobesity effects of CA might be strongly related to its prebiotic effects.

Protective effect of prostaglandin E1 on renal microvascular injury in rats of acute aristolochic acid nephropathy.

BACKGROUND: To investigate the renal microvascular injury in acute aristolochic acid nephropathy (AAN) and the protective effects of prostaglandin E1 (PGE1) in acute AAN. METHODS: Female Sprague-Dawley rats were randomly divided into three groups. The rats in PGE1 group received Caulis Aristolochia manshuriensis (CAM) decoction by gavage for 5 days, and PGE1 was given by vena caudalis before gavage. The rats in model group were gavaged with CAM for 5 days, and the same dose of 0.9% physiologic saline was given by vena caudalis. The rats in control group only received an equal daily volume of saline solution by gavage. Animals were killed at days 3, 5, and 7. Blood urea nitrogen (BUN), serum creatinine, and urinary protein were monitored before killing. Microvascular density was determined by JG12 immunostaining. The expression of angiogenic factor was assessed by vascular endothelial growth factor (VEGF). Tubulointerstitial hypoxia was assessed by hypoxia-inducible factor-1α (HIF-1α) expression. RESULTS: CAM induced a significant decrease in VEGF expression and microvascular density in the kidney tissue, accompanied by a significant increase in HIF-1α, which reduced renal function and increased 24-h urinary protein excretion rates. PGE1 lessened the capillary loss, relieved hypoxia, and protected renal function. No significant pathological changes were found in control rats. CONCLUSION: The renal microvascular injury in acute AAN is severe. PGE1 can significantly ameliorate the renal microvascular injury, relieve hypoxia, and protect renal function.